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Recent pathophysiological models of Parkinson's disease have led to new surgical approaches to treatment including deep brain stimulation (DBS) and lesioning of basal ganglia structures. Various measures of upper limb akinesia were assessed in 6 patients with bilateral DBS of the internal pallidum and 6 with DBS of the subthalamic nucleus. Stimulation improved a number of aspects of motor function, and particularly movement time, and force production. Time to initiate movements, and to perform repetitive movements also improved but less dramatically. Processes indicating preparatory motor processes showed no significant change. Few significant differences were found between the internal pallidum and subthalamic nucleus groups. In general, the effects of DBS closely parallel previous reports of the effects of dopaminergic medication. It is suggested that disrupted pallidal output in Parkinson's disease interferes with the rate, level, and coordination of force production but has little effect on preparatory processes. The similarity of the effects of subthalamic nucleus and internal pallidum stimulation suggests this disrupted outflow is the most important determinant of upper limb akinesia in Parkinson's disease. The effects of DBS were similar to the effects of unilateral pallidal lesions reported elsewhere.

The surgical treatment of intractable epilepsies involving eloquent areas of the cortex is still challenging. Deep-brain stimulation could be an alternative to resective surgery because it can modulate the remote control systems of epilepsy, such as the thalamus and basal ganglia. The surgical experience acquired in the field of movement disorder surgery and the low morbidity of this technic could allow one to apply DBS to intractable epilepsies, such as generalized, motor and bitemporal epilepsies. Here we discuss the main experimental and clinical data reported so far in the literature and taken from our own experience.

Temporal lobe epilepsy (TLE) is the most common form of intractable partial epilepsy in adults. Surgery (lobectomy or amygdalohippocampectomy) is effective in most patients. However, some complications can occur and brain shift, hematoma into the post operative cavity and occulomotor nerve palsy have been reported due to the surgical technic. We report the technique, safety and efficacy of temporal disconnection in nonlesional TLE. Forty-seven patients (18 males, 29 females; handedness: 12 left, 33 right; aged 35 years+/-10; mean duration of epilepsy: 24+/-10 years) underwent temporal disconnection (20 left, 27 right) guided by neuronavigation. Sixteen patients (35 %) underwent additional presurgical evaluation with SEEG. The outcome was assessed using Engel's classification. At the two-year follow-up, 85 % of the patients were seizure-free (Engel I), 26 (58 %) of whom were Ia. Postoperative persistent morbidity included mild hemiparesis (n=1), mild facial paresis (n=1), quadranopsia (n=23) and hemianopia (n=1). Verbal memory worsened in 13 % of cases when the disconnection was performed in the dominant lobe. MRI follow-up showed two cases of nonsymptomatic thalamic or pallidal limited ischemias, two cases of temporal horn-cystic dilatation, one requiring surgical reintervention without sequelae. There was one case of postoperative phlebitis. In the seizure-free patient group, postoperative EEG showed interictal temporal spikes at three months, one year and two years located in the anterior temporal region. Temporal disconnection is effective, prevents the occurrence of subdural cyst and hematomas in the temporal cavity, prevents the occurrence of oculomotor palsy, and limits the occurrence of quadranopsia. However, comparative studies are required to evaluate temporal disconnection as an alternative to lobectomy in nonlesional TLE.

AIM: To evaluate the results of ventral intermediate (Vim) thalamic deep brain stimulation (DBS) in patients with tremor predominant Parkinson's disease (PD) at 6 years post surgery. METHODS: This was a prolonged follow-up study of 38 patients from eight centres who participated in a multicentre study, the 1 year results of which have been published previously. Total scores as well as scores for individual items of the motor part and the disability part of the Unified Parkinson's Disease Rating Scale were used for evaluation. RESULTS: Tremor was still effectively controlled by DBS and appendicular rigidity and akinesia remained stable compared with baseline. Axial scores (speech, gait and postural instability), however, worsened, and in parallel the initial improvement in activities of daily living scores at the 1 year follow-up had disappeared at 6 years, despite sustained improvement of tremor. Remarkably, neither daily doses of dopaminergic medication nor fluctuations and dyskinesias had changed at 6 years compared with baseline in this particular patient group. CONCLUSION: This study confirms that patients with tremor dominant PD who do not present with fluctuations and dyskinesias may have a relatively benign progression of the disease. Vim DBS, although having no effect on akinesia and rigidity, is a relatively lenient surgical procedure and may still have a place for long term symptomatic control of PD tremor in selected patients.

Introduction Depuis la fin du XIX e siecle, la greffe de tissu adipeux autologue a souvent ete utilisee en chirurgie esthetique et reparatrice. La premiere utilisation est decrite en 1893 par Neurer et consistait a transferer une parcelle de tissu adipeux pour une reconstruction faciale. Depuis, la technique a quelque peu evolue grâce a Coleman qui a developpe la lipostructrure. Cette technique est utilisee en chirurgie esthetique dans le comblement des culs-de-sac orbitaires et des cicatrices disgracieuses. Nous rapportons ici un cas clinique ou cette technique est utilisee afin de combler une cavite orbitaire apres expulsion de materiel d’implantation. Observation Un homme, âge de 52 ans, eut une evisceration de l’œil droit pour phtyse du globe post traumatique. Deux semaines plus tard, il presenta une expulsion de la bille d’hydroxyapatite avec des secretions importantes. Les prelevements bacteriologiques mirent en evidence Staphylococcus aureus et Streptococcus anginous . Les secretions persisterent malgre le traitement antibiotique local et general, et anti-inflammatoire non steroidien, motivant l’ablation du materiel d’implantation. Dans un second temps, une greffe d’adipocytes selon la technique de Coleman fut realisee 20 jours plus tard dans le moignon scleral residuel. Les suites furent simples ; la greffe permit de restaurer un volume orbitaire permettant l’adaptation prothetique. Apres 6 mois de recul, la fonte graisseuse secondaire est moderee, et le resultat esthetique satisfaisant. Discussion La technique de Coleman consiste a prelever par lipoaspiration atraumatique des adipocytes en graisse abdominale ou fessiere. Ceux-ci sont ensuite purifies apres centrifugation puis reinjectes au niveau des cicatrices ou des culs-de-sac a combler. En general, ces indications portent sur de petits volumes. Dans notre cas, il s’agissait d’une cavite orbitaire avec un moignon scleral residuel et cloisonne. Ceci peut expliquer le bon resultat esthetique obtenu. En effet, l’atrophie graisseuse postoperatoire est plus importante lorsqu’il n’existe pas de tissu de soutien. Conclusion Cette technique semble plus simple et evite une cicatrice disgracieuse sur le site de prelevement (contrairement a la greffe dermo-graisseuse classique). En revanche, elle est plus couteuse et demande un minimum d’apprentissage.

Artificial brain-machine interfaces (BMIs) represent a prospective step forward supporting or replacing faulty brain functions. So far, several obstacles, such as the energy supply, the portability and the biocompatibility, have been limiting their effective translation in advanced experimental or clinical applications. In this work, a novel 16 channel chronically implantable epicortical grid has been proposed. It provides wireless transmission of cortical recordings and stimulations, with induction current recharge. The grid has been chronically implanted in a non-human primate (Macaca fascicularis) and placed over the somato-motor cortex such that 13 electrodes recorded or stimulated the primary motor cortex and 3 the primary somatosensory cortex, in the deeply anaesthetized animal. Cortical sensory and motor recordings and stimulations have been performed within 3 months from the implant. In detail, by delivering motor cortex epicortical single spot stimulations (1 to 8V, 1 to 10 Hz, 500ms, biphasic waves), we analyzed the motor topographic precision, evidenced by tunable finger or arm movements of the anesthetized animal. The responses to light mechanical peripheral sensory stimuli (blocks of 100 stimuli, each single stimulus being < 1ms and interblock intervals of 1.5 to 4 s) have been analyzed. We found 150 to 250ms delayed cortical responses from fast finger touches, often spread to nearby motor stations. We also evaluated the grid electrical stimulus interference with somatotopic natural tactile sensory processing showing no suppressing interference with sensory stimulus detection. In conclusion, we propose a chronically implantable epicortical grid which can accommodate most of current technological restrictions, representing an acceptable candidate for BMI experimental and clinical uses.

Introduction Alors que le taux de lymphomes malins non-Hodgkiniens (LMNH) diagnostiques ne cesse d’augmenter dans le monde, le LMNH a localisation orbitaire est une tumeur relativement rare et de diagnostic difficile. Le but de cette etude est d’analyser les cas de LMNH a localisation conjonctivo-orbitaire examines, dans le service d’Ophtalmologie du CHU d’Amiens, au cours de ces 20 dernieres annees. Materiel et methodes Nous avons mene une etude retrospective des cas de lymphomes a localisation conjonctivo-orbitaire diagnostiques dans le Service d’Ophtalmologie d’Amiens entre 1982 et 2002. Les comptes rendus anatomopathologiques de 22 cas ont ete etudies, notamment le mode de survenue, la description clinique, radiologique, le mode diagnostique, les resultats anatomo-pathologiques et le type de traitement de ces tumeurs. Resultats Tous les LMNH etaient de type B. Ils etaient de bas grade de malignite dans 17 cas, isoles dans 22 cas, primitifs, de localisation orbitaire dans 9 cas et de type indolent. Discussion Le clinicien se heurte souvent a des lesions insidieuses dont l’acces a la biopsie est souvent difficile, retardant le diagnostic. Le premier diagnostic differentiel a evoquer est l’inflammation orbitaire chronique anciennement appelee pseudo-tumeur inflammatoire. Seule une biopsie orbitaire permet d’affirmer le diagnostic de LMNH. Conclusion Les nouveaux moyens diagnostiques tels que l’immunohistochimie et la genetique permettent de depister de plus en plus de LMNH, meme si leur histoire clinique peut encore faire errer le diagnostic De plus, des therapeutiques de plus en plus ciblees sur le type immunohistochimique du LMNH semblent donner des resultats tres prometteurs. Des etudes sont encore en cours.

Brain pathology is a perfect application field for nanotechnologies supporting the concept of nanomedicine. It implies the use of nanosized tools for diagnosis and therapy and finally the switch to nanosized disease. A good illustration is the synergistic association of functional neurosurgery to micro/nanotechnologies. The developments around electrostimulation are a good example of the lower invasivity and better therapeutical efficacy that can be achieved. Nanolevel disease detection and therapy dramatically modifies medical philosophy as well as practice. The demonstration of the validity of the concept of nanomedicine has to be done carefully and this period of validation is a precious time to solve ethical problems. Ethical issues include the problem of disease detection in “healthy patients”; the non medical use of nanotechnologies, and the acceptance of what could be a potentially uncontrollable major modification of the human body. All these items are used against nanotechnologies, thus it will be crucial to inform the public about the state of the art in nanomedicine and about the existing regulations. National and European regulations should be adequate for nanomedicine, provided there is progressive integration instead of a conservative attitude blocking experiments and progress. The European research community has a good opportunity to do that.

Resume Objectifs Discuter l’apport des techniques d’imagerie de perfusion par RMN dans le diagnostic initial et le suivi de l’evolution des tumeurs cerebrales, gliales en particulier. Methodologie La technique utilisee est la technique de premier passage apres injection intra-veineuse d’un embole de produit de contraste IRM, dont les avantages et les limites sont decrits. Elle permet la mesure d’un rapport (rVSCmax) entre le volume sanguin cerebral en zone lesionnelle et en zone de tissu normal. Resultats Cette technique a ete appliquee a une serie de patients porteurs de tumeurs cerebrales : elle apporte des donnees interessantes dans le diagnostic differentiel de lesions comme les lymphomes ou les astrocytomes pilocytiques et dans le grading des gliomes. Discussion, Conclusion Sur le plan methodologique, la quantification precise de ces parametres de perfusion et leur interpretation en terme de neovascularisation est discutee. Sur le plan clinique, ces mesures de rVSCmax sont plus informatives que ne l’est qualitativement l’appreciation de la prise de contraste. Elles devraient trouver leur place dans le grading tumoral, en particulier dans les oligodendrogliomes.

To determine the perfusion-sensitive characteristics of cerebral dural metastases and compare them with the data on meningiomas. Twenty-two patients presenting with dural tumor underwent conventional and dynamic susceptibility-contrast MR imaging: breast carcinoma metastases, two patients; colorectal carcinoma metastasis, one patient; lung carcinoma metastasis, one patient; Merkel carcinoma metastasis, one patient; lymphoma, one patient; meningiomas, 16 patients. The imaging characteristics were analyzed using conventional MR imaging. The cerebral blood volume (CBV) maps were obtained for each patient and the relative CBV (rCBV) in different areas was calculated using the ratio between the CBV in the pathological area (CBVp) and in the contralateral white matter (CBVn). The differentiation between a meningioma and a dural metastasis can be difficult using conventional MR imaging. The rCBVs of lung carcinoma metastasis (1 case: 1.26), lymphoma (1 case: 1.29), breast carcinoma metastasis (2 cases: 1.50,1.56) and rectal carcinoma metastasis (1 case: 3.34) were significantly lower than that of meningiomas (16 cases: mean rCBV = 8.97±4.34, range 4–18). Merkel carcinoma metastasis (1 case: 7.56) showed an elevated rCBV, not different from that of meningiomas. Dural metastases are sometimes indistinguishable from meningiomas using conventional MR imaging. rCBV mapping can provide additional information by demonstrating a low rCBV which may suggest the diagnosis of metastasis.

Resume Le traitement neurochirurgical de la maladie de Parkinson (MP) par stimulation cerebrale profonde (SCP) a ete introduit pour la premiere fois en 1987. Il a depuis lors connu un developpement considerable lie non seulement aux limites du traitement medicamenteux mais egalement a l’amelioration des techniques d’imagerie cerebrale et aux progres realises dans la connaissance du fonctionnement des ganglions de la base. Le tremblement resistant au traitement medicamenteux et les complications motrices liees a la levodopa constituent les principales indications de SCP dans la MP. Le noyau ventral intermediaire du thalamus (Vim) fut la premiere cible utilisee pour le traitement des tremblements severes. L’inconstance des effets observes sur la rigidite et l’akinesie parkinsoniennes ainsi que sur les dyskinesies liees a la levodopa limite les indications de la stimulation du Vim au traitement du tremblement essentiel invalidant. Le pallidum interne et le noyau subthalamique sont les deux autres cibles indiquees dans le traitement des formes severes de MP. La stimulation du pallidum interne est indiquee chez des patients presentant des dyskinesies invalidantes. Elle a l’avantage de pouvoir etre realisee de facon bilaterale, sans complication arthrique, posturale ou neuropsychologique majeure par rapport aux pallidotomies. La taille et la complexite de fonctionnement de la structure pallidale sont vraisemblablement a l’origine de la variabilite des effets observes et des resultats obtenus par differentes equipes. Le noyau subthalamique constitue la cible de reference pour le traitement neurochirurgical de la MP. Sa stimulation chronique permet de controler l’ensemble des symptomes de la triade parkinsonienne. L’amelioration de l’etat moteur permet de reduire considerablement le traitement medicamenteux et, par ce mecanisme, les dyskinesies liees a la levodopa. Des complications severes peuvent survenir dans 2 a 4 p. 100 des cas. Il s’agit d’infections sur materiel implante et de contusions hemorragiques. Ces techniques neurochirurgicales ne peuvent etre mises en œuvre que par des equipes pluridisciplinaires regroupant des neurochirurgiens experts en stereotaxie fonctionnelle, des neurologues specialises dans les troubles du mouvement, des neuroradiologues, des neuropsychologues et des kinesitherapeutes. Ce sont des techniques sophistiquees dont l’indication doit etre posee avec discernement.

We have developed a convenient and sensitive method for the quantification of RNA in samples from microbiopsies. This procedure is especially suitable for quantitating very small amounts of RNA in largescale biological samples. This method, using a microarray-spotting facility for the study of multigenic expression, entails the hybridization of a DNA probe with RNA spotted at high density on nylon membrane. Furthermore, with this procedure, the reproducibility, sensitivity, and accuracy of the assay are notably improved as compared to current methods.

Background: In a previous study on a consecutive series of 62 patients with PD, the authors showed that bilateral subthalamic or pallidal continuous high-frequency deep brain stimulation (DBS) affects neither memory nor executive functions 3 to 6 months after surgery. Objective: To investigate the specific effects of DBS by comparing the performance of patients with the stimulator turned “on” and “off.” Methods: The performance of 56 patients on clinical tests of executive function was compared after 3 and 12 months of DBS of the subthalamic nucleus (STN; n = 48) or the internal globus pallidus (GPi; n = 8) with the stimulator “on” or “off.” Global intellectual efficiency, verbal learning, and mood were also evaluated with the stimulator “on.” The performance of another group of 20 patients was compared after 6 months of DBS of the STN (n = 15) or the GPi (n = 5) with the stimulator “on” or “off” on more experimental tests recently shown to be more sensitive to l-dopa therapy. Results: When the stimulator was “on,” STN patients showed a mild but significant improvement in psychomotor speed and working memory. In comparison with the presurgical state, STN patients had no cognitive deficit at 12 months, except for lexical fluency. There was no differential effect of STN or GPi stimulation. Conclusions: 1) The specific effect of DBS seems to mimic the action of l-dopa treatment in the cognitive as in the motor domain; 2) the surgery associated with DBS does not appear to affect the cognitive performance of patients with PD 12 months later, except for a mild deficit in lexical fluency.

Neurosurgery is in essence a field of application development for robots, based on multimodal image guidance. Specific motorized tools have already been developed and routinely applied in stereotaxy to position a probe holder or in conventional neurosurgery to hold a microscope oriented towards a given target. The potentialities of these approaches have triggered industrial developments which are now commercially available. These systems use databases, primarily coming from multimodal numerical images from X-ray radiology to magnetic resonance imaging. These spatially encoded data are transferred through digital networks to workstations where images can be processed and surgical procedures are pre-planned, then transferred to the robotic systems to which they are connected. We have been using a stereotaxic robot since 1989 and a microscope robot since 1995 in various surgical routine procedures. The future of these applications rely mainly on the technical progress in informatics, about image recognition to adapt the pre-planning to the actual surgical situation, to correct brain shifts (for instance), about image fusion, integrated knowledge such as brain atlases, as well as virtual reality. The future developments, covering surgical procedure, research and teaching, are sure to be far beyond our wildest expectations.

We studied the effects--on parkinsonian signs, on levodopa-induced dyskinesias, and on levodopa response--of acute experimental high-frequency stimulation of the internal pallidum (GPi) during off-drug and on-drug phases. Thirteen quadripolar electrodes were evaluated in 8 patients with Parkinson's disease (PD). Stimulation of the most ventral contacts, lying at the ventral margin of or just below the GPi, led to pronounced improvement in rigidity and a complete arrest of levodopa-induced dyskinesias. The antiakinetic effect of levodopa was also blocked and the patients became severely akinetic. Stimulation of the most dorsal contacts, lying at the dorsal border of the GPi or inside the external pallidum, usually led to moderate improvement of off-drug akinesia and could also induce dyskinesias in some patients. When using an intermediate contact for chronic stimulation, a good compromise between these opposite effects was usually obtained, mimicking the effect of pallidotomy. We conclude that there are at least two different functional zones within the globus pallidus, at the basis of a different pathophysiology of the cardinal symptoms of PD. The opposite effects may explain the variable results of pallidal surgery reported in the literature and may also largely explain the paradox of PD surgery. A possible anatomical basis for these differential functional effects could be a functional somatotopy within the GPi, with the segregation of the pallidofugal fibers from the outer portion of the GPi, on one hand, forming the ventral ansa lenticularis and from the inner portion of the GPi, on the other hand, forming the dorsal lenticular fasciculus.

A scanning tunneling microscopy (STM) study is presented for the growth of Ni films on Re (0001) at 300 K. A Ni(111) wedge with a slope of 5 ML cm−1 was prepared under identical conditions. STM images were recorded in ultrahigh vacuum at 300 K on areas of the wedge with constant coverage. Nearly ideal two-dimensional growth is observed for the first three layers. The second layer grows only after the first layer is 90% complete. For films with thicknesses 2 < d ≤ 9 ML, a perfect hexagonal dislocation network which matches the known 910 misfit of Ni(111) with respect to Re (0001) is observed across 600 × 600 nm2 images. The corrugation of ∼0.3 A, observed at 3 ML, decreases with an increasing number of layers and vanishes completely around 10 ML. The dislocation pattern does not seem to be disturbed by the presence of monoatomic steps. A characteristic change in the pattern of the dislocation network is observed from 1 to 3 ML.

Introduction Le lymphome malin non hodgkinien (LMNH) conjonctivo-orbitaire est une tumeur relativement rare de diagnostic difficile. L’attitude therapeutique face aux formes indolentes tend a se modifier, et le developpement de l’immunotherapie y contribue. Nous rapportons deux cas de patients traites par rituximab (anticorps anti-CD20). Observation Deux femmes, âgees respectivement de 50 ans et 59 ans, presenterent un LMNH indolent, isole et de bas grade de malignite : l’un, conjonctival de type MALT et l’autre, orbito-palpebral de type A selon la WFC, folliculaire a petites cellules. L’immunohistochimie montrait un marquage diffus pour l’anticorps anti-CD20. Les patientes recurent en 1 re intention une monotherapie de rituximab par voie intraveineuse, debutee en decembre 2000, a raison de 375 mg/m 2 , en 4 injections a 1 semaine d’intervalle. Aucun effet indesirable majeur ne fut constate. Les patientes sont en remission complete depuis la fin du traitement, soit un recul de 4 ans. Elles sont toujours sous suivi hematologique et ophtalmologique regulier. Conclusion Le rituximab (Mabthera ® ) offre une alternative non negligeable dans le traitement des LMNH orbitaires indolents. Son efficacite est surtout documentee dans les LMNH folliculaires ou chez les patients a rechutes. Celles-ci seraient un peu plus frequentes dans le type MALT. Par ailleurs, ce traitement presente une faible toxicite hematologique et est generalement bien tolere.

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.

A wireless 64-channel ElectroCorticoGram (ECoG) recording implant named WIMAGINE(®) has been designed for clinical applications. This active implantable medical device is able to record ECoG on 64 electrodes with selectable gain and sampling frequency, with less than 0.7 µVRMS input referred noise in the [0.5 Hz - 300 Hz] band. It is powered remotely through an inductive link at 13.56 MHz, communicates wirelessly on the MICS band at 402-405 MHz with a custom designed base station connected to a PC and complies with the regulations applicable to class III AIMD. The design of the housing and the antenna have been optimized to ease the surgery and to take into account all the requirements of a clinical trial in particular patient safety and comfort. The main features of this WIMAGINE(®) implantable device and its architecture will be presented, as well as its performances and in vivo validations.

International audience; Access to cerebral tissue is essential to better understand the molecular mechanisms associated with neurodegenerative diseases. In this study, we present, for the first time, a new tool designed to obtain molecular and cellular cerebral imprints in the striatum of anesthetized monkeys. The imprint is obtained during a spatially controlled interaction of a chemically modified micro-silicon chip with the brain tissue. Scanning electron and immunofluorescence microscopies showed homogeneous capture of cerebral tissue. Nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) analysis of proteins harvested on the chip allowed the identification of 1158 different species of proteins. The gene expression profiles of mRNA extracted from the imprint tool showed great similarity to those obtained via the gold standard approach, which is based on post-mortem sections of the same nucleus. Functional analysis of the harvested molecules confirmed the spatially controlled capture of striatal proteins implicated in dopaminergic regulation. Finally, the behavioral monitoring and histological results establish the safety of obtaining repeated cerebral imprints in striatal regions. These results demonstrate the ability of our imprint tool to explore the molecular content of deep brain regions in vivo. They open the way to the molecular exploration of brain in animal models of neurological diseases and will provide complementary information to current data mainly restricted to post-mortem samples.

Based on Benabid's experimental and clinical findings that low-frequency (50 Hz) electrical stimulation of the ventral intermediate thalamic nucleus may increase tremor, while higher frequencies (> 100 Hz) lead to suppression of the tremor, we implanted a stimulation electrode in 33 thalami among 27 patients. Six patients were implanted bilaterally. 23 suffered from Parkinson's disease, 4 from essential tremor. All patients had a drug-resistant tremor. The Vim target was calculated based on stereotactic ventriculography. An intra-operative neurophysiological target control was performed on all patients. After a monopolar (12 thalami) or quadripolar (21 thalami) lead was implanted we then connected it to a percutaneous extension lead. In the days following the surgery a test stimulation was performed. In all but one patient stimulation resulted in a suppression of the tremor. In a second procedure, a pulse generator (ITREL II; MEDTRONIC) was implanted and connected subcutaneously to the thalamic lead. After implantation of the pulse generator all patients stimulate chronically while some turn off the stimulator at night. In 21 thalami total suppression of tremor was observed, 6 showed major improvement, 4 only minor improvement. There was no significant effect on any other existing symptom of Parkinson's disease. Due to the proximity of Vim to the sensory thalamus the majority of the patients (27 thalami) report slight temporary paraesthesias when the pulse generator is turned on. Two report permanent paraesthesias when stimulation is on. In 4 cases a slight dysarthria occurs under stimulation. In 2 the dysarthria is marked. In one case dysequilibrium occurs under stimulation. All these side effects are reversible when stimulation is turned off. In 3 patients, the lead was displaced due to an insufficient lead fixation, thus making a second procedure necessary to correct the electrode position. We had one complication due to bleeding at the burr hole side. Follow-up ranges from 3 to 48 months. So far in no cases has the effect of stimulation worn off. In conclusion we regard Vim neurostimulation as an effective and safe alternative to conventional thalamotomy and recommend that it should be considered in cases in which drug therapy has failed to affect Parkinsonian or essential tremor. Moreover, we believe that this procedure is a less invasive and equally efficient alternative to classic thalamotomy and thus should be given preference.

International audience; OBJECTIVE: Although electrophysiologic dysfunction of the subthalamic nucleus is putative, deep brain stimulation of this structure has recently been reported to improve obsessions and compulsions. In Parkinson disease, sensorimotor subthalamic neurons display high-frequency burst firing, which is considered as an electrophysiologic signature of motor loop dysfunction. We addressed whether such neuronal dysfunction of the subthalamic nucleus also exists in the nonmotor loops involved in patients with obsessive-compulsive disorder. METHODS: We compared the neuronal activity of the subthalamic nucleus recorded in 9 patients with obsessive-compulsive disorder with that of 11 patients with Parkinson disease measured during intraoperative exploration for deep brain stimulation. RESULTS: The mean subthalamic neuron discharge rate was statistically lower in patients with obsessive-compulsive disorder than in patients with Parkinson disease (20.5 ± 11.0 Hz, n = 100 and 30.8 ± 15.6 Hz, n = 93, respectively, p < 0.001). The relative proportion of burst neurons did not differ significantly between the 2 diseases (75% vs 73%). Interestingly, burst neurons were predominantly left-sided in obsessive-compulsive disorder. INTERPRETATION: The recording of burst neurons within the nonmotor subthalamic nucleus in patients with obsessive-compulsive disorder is a novel finding that suggests the existence of deregulation of the nonmotor basal ganglia loop, possibly left-sided. Potentially, burst activity might interfere with normal processes occurring within nonmotor loops.

Appetite modulation in conjunction with enhancing metabolic rate with hypothalamic lesions has been widely documented in animal and even in humans. It appears these effects can be reproduced by DBS, and the titratability and reversibility of this procedure, in addition to well established safety profile, make DBS an appealing option for obesity treatment. Targeting the hypothalamus with DBS has already been shown to be feasible and potentially effective in managing patients with intractable chronic cluster headache [26]. The surgical risk however must be cautiously taken into account when targeting the hypothalamus, where some mortality cases have been reported when targeting the posterior part [34]. The development of new surgical approach will probably reduce this surgical risk. Moreover, the role of functional neurosurgery in obesity is not a new idea. In fact, LH was targeted in obese humans with electrocoagulation more than 30 years ago, resulting in significant yet transient appetite suppression and slight weight reduction [36]. All those elements have made possible the recent regain of interest in DBS for morbid obesity and open an exciting new area of research in neurosurgery and endocrinology.

It is not rare for a neurosurgeon to be surprised when he observes that making lesions or a resection in a patient’s brain does not induce necessarily a deficit, or at least an observable deficit. This observation is common and without it neurosurgery in general, and functional neurosurgery in particular, would not be possible to perform. Trying to understand how this could happen leads quickly to the conclusion that those circuits are not fully necessary and can be deactivated or even destroyed without a significant damage to the functionality of the brain. Several questions are raised by this observation. Are these lesions or deactivations really without any effect? Why does this happen? Could it be that those circuits are embryological remnants, without real utility? Could it be that they have been added by evolution to improve the sophistication of actions, particularly of movement? Evolution does not know how to remove previously added structures.

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.

Functional neurosurgery for movement disorders started in the early 1940s. It was mainly based on lesion (ablative surgery) using various methods of destruction aimed at various targets on the basis of either theoretical anatomo-functional considerations or anecdotal observations, the most famous being the introduction of thalamotomy and pallidotomy following Irving Cooper’s observations of an accidental ligature of the anterior choroidal artery. Later, trial and error based methods, associated to electrophysiology, led to the definition of an ideal target defined as the magnocellular part of the ventral intermedius (Vim) nucleus of the thalamus. This became the standard target and electrocoagulation the standard surgical technique to treat tremor, both in Parkinson’s disease (PD) and in essential tremor (ET). The most frequently improved symptom was tremor, with good and long lasting results, with two main drawbacks. (i) The effects did not last and needed reoperation when the lesion was well placed but too small. (ii) Side effects could be observed when the lesion was too large, involving peri-target structures, particularly the internal capsule which led to motor deficits, not always reversible. Moreover, bilateral surgery, often required by the clinical status of the patient, was too often associated with neurocognitive deficits.

Temporal lobe epilepsy (TLE) is the most common form of intractable partial epilepsy in adults. Surgery (lobectomy or amygdalohippocampectomy) is effective in most patients. However, some complications can occur and brain shift, hematoma into the post operative cavity and occulomotor nerve palsy have been reported due to the surgical technic. We report the technique, safety and efficacy of temporal disconnection in nonlesional TLE. Forty-seven patients (18 males, 29 females; handedness: 12 left, 33 right; aged 35 years+/-10; mean duration of epilepsy: 24+/-10 years) underwent temporal disconnection (20 left, 27 right) guided by neuronavigation. Sixteen patients (35 %) underwent additional presurgical evaluation with SEEG. The outcome was assessed using Engel's classification. At the two-year follow-up, 85 % of the patients were seizure-free (Engel I), 26 (58 %) of whom were Ia. Postoperative persistent morbidity included mild hemiparesis (n=1), mild facial paresis (n=1), quadranopsia (n=23) and hemianopia (n=1). Verbal memory worsened in 13 % of cases when the disconnection was performed in the dominant lobe. MRI follow-up showed two cases of nonsymptomatic thalamic or pallidal limited ischemias, two cases of temporal horn-cystic dilatation, one requiring surgical reintervention without sequelae. There was one case of postoperative phlebitis. In the seizure-free patient group, postoperative EEG showed interictal temporal spikes at three months, one year and two years located in the anterior temporal region. Temporal disconnection is effective, prevents the occurrence of subdural cyst and hematomas in the temporal cavity, prevents the occurrence of oculomotor palsy, and limits the occurrence of quadranopsia. However, comparative studies are required to evaluate temporal disconnection as an alternative to lobectomy in nonlesional TLE.

OBJECTIVE: We studied the effects of subthalamic nucleus (STN) stimulation vs levodopa on freezing of gait (FOG) and gait impairments in a large consecutive series of patients with Parkinson disease with bilateral STN stimulation. METHODS: One hundred twenty-three patients performed the Stand Walk Sit Test before and 1 year after surgery both off and on levodopa and off and on stimulation. RESULTS: Before surgery, 25 patients displayed FOG episodes and 48 were unable to complete the Stand Walk Sit Test when off levodopa. Both symptoms were alleviated by levodopa. After surgery, STN stimulation reproduced the improvement induced by levodopa before surgery in all but two patients with FOG and five others unable to walk. In 11 patients, FOG or inability to perform the test first occurred after surgery. In all patients but those experiencing FOG during the Stand Walk Sit Test before surgery, the benefit of STN stimulation did not reach that of levodopa before surgery. In patients with FOG before surgery, the effect of STN stimulation did not differ from that of levodopa either before or after surgery. CONCLUSIONS: Overall, subthalamic nucleus stimulation improved levodopa-responsive freezing of gait in most patients, although it was not always as effective as levodopa to improve gait impairments. In addition, surgery can induce gait problems in some patients.

The surgical treatment of intractable epilepsies involving eloquent areas of the cortex is still challenging. Deep-brain stimulation could be an alternative to resective surgery because it can modulate the remote control systems of epilepsy, such as the thalamus and basal ganglia. The surgical experience acquired in the field of movement disorder surgery and the low morbidity of this technic could allow one to apply DBS to intractable epilepsies, such as generalized, motor and bitemporal epilepsies. Here we discuss the main experimental and clinical data reported so far in the literature and taken from our own experience.

Since the end of the 19th century, autologous fat grafting has often been used in plastic surgery. The first use was described in 1893 by Neurer and consisted in transferring a piece of fat tissue for facial reconstruction. Since then, this technique has evolved somewhat thanks to Coleman, who developed lipostructure. This technique is used in plastic surgery in the filling of orbital cul-de-sacs and unsightly scars. We report a clinical case where this technique was used to fill an anophthalmic socket after extrusion of an orbital implant.A 52-year-old man had evisceration of the right eye for ocular phthisis bulbi after injury to the eye. Two weeks later, he presented an expulsion of the hydroxyapatite eyeball with significant secretions. The bacteriological samples showed Staphylococcus aureus and Streptococcus anginous infection. Despite local and general antibiotic treatment and anti-inflammatory drugs, the secretions persisted. The implant material was initially ablated. Twenty days later, adipocyte was grafted in the residual scleral stump using the Coleman technique. Follow-up showed no complications; the adipocyte grafting made it possible to restore orbital volume so that the prosthesis could be adapted. After 6 months, secondary atrophy is moderate and a good esthetic result was obtained.The Coleman technique consists in taking adipocytes in abdominal or buttocks fat with nontraumatic liposuction. This is purified after centrifugation, then reinjected into the scars or the orbital cul-de-sacs to be filled. In general, these indications relate to small volumes. In our case, the procedure involved an anophthalmic socket with residual septated scleral tissue. This can explain the good esthetic result obtained. Indeed, the fat atrophy after surgery is more significant when there is no supporting tissue.This technique seems simpler and avoids an unsightly scar on the harvest site (contrary to the traditional dermis-fat graft). On the other hand, it is more expensive and requires a minimum of training.

The present paper is devoted to suppression of spurious signals (artifacts) in records of neural activity during deep brain stimulation. An approach based on a nonlinear adaptive model with self‐oscillations is proposed.

High frequency stimulation (HFS) has become the main alternative to medical treatment, due to its reversibility, adaptability, and low morbidity. Initiated in the thalamus (Vim) for the control of tremor, HFS has been applied to the Pallidum (GPi), and then to the subthalamic nucleus (STN), suggested by experiments in MPTP monkeys. STN-HFS is highly efficient on tremor, rigidity and bradykinesia and is now widely applied. Criteria for success are correct patient selection and precise electrode placement. The best outcome predictor is the response to Levodopa. The mechanisms of action might associate inhibition of cell firing, jamming of neuronal message and exhaustion of synaptic neurotransmitter release. The inhibition of glutamate STN release could be neuroprotective on nigral cells. Animal experiments support this hypothesis, not contradicted by the long-term follow up of patients. Neuroprotection might have considerable impact on the management of PD patient and warrants clinical trials.

Robots are the tools for taking advantage of the skills of computers in achieving complicated tasks. This has been made possible owing to the "numerical image explosion" which allowed us to easily obtain spatial coordinates, three dimensional reconstruction, multimodality imaging including digital subtraction angiography (DSA), computed tomography (CT), magnetic resonance imaging (MRI) and magneto encephalography (MEG), with high resolution in space, time, and tissue density. Neurosurgical robots currently available at the operating level are being described. Future evolutions, indications and ethical aspects are examined.

High frequency stimulation of the subthalamic nucleus (STN) is an alternative but expensive neurosurgical treatment for parkinsonian patients with levodopa induced motor complications.To assess the safety, clinical effects, quality of life, and economic cost of STN stimulation.We conducted a prospective multicentre study in 95 consecutive Parkinson's disease (PD) patients receiving bilateral STN stimulation and assessed its effects over 12 months. A double blind randomised motor evaluation was carried out at 3 month follow up, and quality of life, self care ability, and predictive factors of outcome following surgery were assessed. The cost of PD was estimated over 6 months before and after surgery.The Unified Parkinson's Disease Rating Scale (UPDRS) motor score improved by 57% (p0.0001) and activities of daily living improved by 48% (p0.0001) at 12 month follow up. Double blind motor scoring improved by 51% at 3 month follow up (p0.0001). The total PD Quality of Life Questionnaire (PDQL-37) score improved by 28% (p0.001). The better the preoperative motor score after a levodopa challenge, the better the outcome after STN stimulation. Five patients developed an intracerebral haematoma during electrode implantation with permanent after effects in two. The 6 month costs of PD decreased from 10,087 euros before surgery to 1673 euros after surgery (p0.0001) mainly because of the decrease in medication. These savings allowed a return on the procedure investment, estimated at 36,904 euros over 2.2 years.STN stimulation has good outcomes with relatively low risk and little cost burden in PD patients with levodopa induced motor complications.

Although the number of non-Hodgkin's lymphoma (NHL) cases continues to grow throughout the world, orbital NHL is still a rare tumor that is difficult to diagnose. The objective of our study was to analyze the different orbital NHLs diagnosed in our Ophthalmology Department during the last 20 years.[corrected] We conducted a retrospective study of conjunctive-orbital lymphomas diagnosed in the Amiens Ophthalmology Department between 1982 and 2002. The pathological reports of 22 cases were investigated, notably the mode of onset, the clinical and radiological description, the diagnostic mode, pathological results, and the type of treatment provided for these tumors.Every NHL was type B. They were for the most part low grade in terms of malignancy, isolated, primitive, orbital and inactive.Insidious, slow-growing lesions are often found, and biopsy can be difficult. This may explain delayed diagnosis. The first differential diagnosis is inflammatory pseudotumor. Only a good biopsy can confirm the diagnosis of NHL.New immunohistochemistry and genetic diagnostic methods make it increasingly possible to screen for NHL, even if the clinical history can be misleading. Moreover, treatments that are more and more precisely targeted to the immunohistochemical type of NHL seem to be giving very promising results. Several studies are ongoing.

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Orbital non-Hodgkin's lymphoma is a rare tumor whose diagnosis is often difficult. Treatment of latent lymphoma have been changing because of progress in immunotherapy.We report two patients treated with rituximab (antibody anti-CD20). Two women, 50 and 59 years old, presented low-grade, IE-stage lymphoma. One was conjunctival MALToma, the other was orbitopalpebral, type A, of WFC classification, follicular, with small cells. Immunohistochemistry showed a diffused marking for Ac anti-CD20. Both patients received intravenous rituximab as a first treatment in December 2000, 375 mg/m2, four injections per week. We did not note any major undesirable effects. Both have been in complete remission for 4 years. These patients continue to be followed up.Rituximab's efficacy has been proved mainly in follicular LMNH or in recurrent forms. The recurrence may be more frequent in MALT lymphoma. This medical treatment has low hematologic toxicity.Rituximab offers an alternative for low-grade lymphoma treatment that is well tolerated by the patient.

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.

Since its advent in 1993, high frequency stimulation (HFS) of the subthalamic nucleus (STN) has rapidly developed into the most commonly practiced surgical procedure for the treatment of Parkinson's Disease (PD). Although its exact mechanism of action, be it through an inhibitory depolarization block, desynchronization of neuronal circuits or other means, is not clear, the efficacy and safety of the technique are now well established. HFS of the STN improves the motor function by at least 60%, drastically reduces the levodopa requirement and significantly improves the quality of life in PD. This review updates the recent concepts on the pathophysiology of PD and analyses the basic science principles underlying the clinical practice of the STN HFS. The evolution of the surgical technique and long-term patients' outcome are further discussed.

International audience; The aim of this fMRI study was to evaluate the motor reorganization (cerebral plasticity) and the risk of motor deficit in patients presenting with tumors and vascular malformations, within the framework of their pre-surgical planning. Functional MR imaging data was obtained from 17 patients. Ten patients (seven with tumors and three with vascular malformations) presented with motor reorganization. The results of the present study suggest that the evaluation of the cerebral reorganization is an essential step in predicting the risk of motor deficit in patients having surgical indication for treatment. Furthermore, the cerebral reorganization constitutes an important factor for surgical decision.

Factor XIII (FXIII) deficiency is a rare autosomal recessive congenital disorder of haemostasis, associated with a high risk of intracranial haemorrhage. Intracranial haemorrhage can result in neurological sequelae including seizure disorders. In some cases, medically intractable epilepsy led to epilepsy surgery. Little has been reported on the management of FXIII deficiency during surgery, and there is only a few data on the management, safety and efficacy of epilepsy surgery in the patients with haemostatic disorder. We report here an epilepsy neurosurgery in a case of severe FXIII deficiency.

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.To determine in Parkinson's disease (PD) patients using positron emission tomography (PET) and [11C]-Raclopride, whether STN stimulation induces a striatal DA release.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.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.STN stimulation does not produce significant variations of striatal DA release as assessed by PET and [11C]-Raclopride.

In order to assess the impact of bilateral subthalamic nucleus (STN) stimulation in PD on quality of life, the PD Quality of Life questionnaire was assessed in 60 consecutive patients with PD before surgery and 12 months after surgery. All aspects of quality of life, including motor (+48%), systemic (+34%), emotional (+29%), and social (+63%) dimensions, significantly improved with long-term STN stimulation.