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Objective: To assess the efficacy of epidural motor cortex stimulation (MCS) on dystonia, spasticity, pain, and quality of life in patients with dystonia secondary to a focal basal ganglia (BG) lesion., Methods: In this double-blind, crossover, multicenter study, 5 patients with dystonia secondary to a focal BG lesion were included. Two quadripolar leads were implanted epidurally over the primary motor (M1) and premotor cortices, contralateral to the most dystonic side. The leads were placed parallel to the central sulcus. Only the posterior lead over M1 was activated in this study. The most lateral or medial contact of the lead (depending on whether the dystonia predominated in the upper or lower limb) was selected as the anode, and the other 3 as cathodes. One month postoperatively, patients were randomly assigned to on- or off-stimulation for 3 months each, with a 1-month washout between the 2 conditions. Voltage, frequency, and pulse width were fixed at 3.8 V, 40 Hz, and 60 μs, respectively. Evaluations of dystonia (Burke-Fahn-Marsden Scale), spasticity (Ashworth score), pain intensity (visual analog scale), and quality of life (36-Item Short Form Health Survey) were performed before surgery and after each period of stimulation., Results: Burke-Fahn-Marsden Scale, Ashworth score, pain intensity, and quality of life were not statistically significantly modified by MCS., Conclusions: Bipolar epidural MCS failed to improve any clinical feature in dystonia secondary to a focal BG lesion., Classification of Evidence: This study provides Class I evidence that bipolar epidural MCS with the anode placed over the motor representation of the most affected limb failed to improve any clinical feature in dystonia secondary to a focal BG lesion.

The pedunculopontine area (PPNa) including the pedunculopontine and cuneiform nuclei, belongs to the mesencephalic locomotor region. Little is known about the oscillatory mechanisms underlying the function of this region in postural and gait control. We examined the modulations of the oscillatory activity of the PPNa and cortex during stepping, a surrogate of gait, and stance in seven Parkinson's disease patients who received bilateral PPNa implantation for disabling freezing of gait (FOG). In the days following the surgery, we recorded behavioural data together with the local field potentials of the PPNa during sitting, standing and stepping-in-place, under two dopaminergic medication conditions (OFF and ON levodopa). Our results showed that OFF levodopa, all subjects had FOG during step-in-place trials, while ON levodopa, stepping was effective (mean duration of FOG decreasing from 61.7±36.1% to 7.3±10.1% of trial duration). ON levodopa, there was an increase in PPNa alpha (5-12 Hz) oscillatory activity and a decrease in beta (13-35 Hz) and gamma (65-90 Hz) bands activity. PPNa activity was not modulated during quiet standing and sitting. Our results confirm the role of the PPNa in the regulation of gait and suggest that, in Parkinson disease, gait difficulties could be related to an imbalance between low and higher frequencies.

Purpose: Failure of anterior temporal lobectomy for temporal lobe epilepsy has raised the question of insular cortex involvement in these seizures. Because of difficulties in exploring the insula with invasive electroencephalography (EEG) recordings, only few studies have been performed and this question remains unanswered., Methods: Here, we studied 17 patients who underwent surgery for drug-resistant temporal lobe epilepsy, explored with intracerebral electrodes, with at least one electrode coplanar to the insula. We analyzed seizure propagation patterns from temporal lobe structures to the insula, and their effect on outcome. We used an objective measure of the epileptogenicity of the insula for individual cases and group analysis between patients who were seizure-free after surgery and the others., Key Findings: All temporal lobe seizures propagated to the insular cortex, with a shorter propagation delay in the case of mesiolateral temporal lobe seizures, thus supporting the existence of a perilimbic network. Epileptogenicity of the insular cortex was not a prognostic factor for outcome after surgery., Significance: Insular involvement in temporal lobe seizure is not per se a prognostic factor for surgical outcome. Prognosis may be correlated with larger epileptogenic zones that our stereoelectroencephalography spatial sampling could have underestimated., (Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.)

Apathy is one of the most common symptoms encountered in Parkinson's disease, and is defined as a lack of motivation accompanied by reduced goal-directed cognition, behaviour and emotional involvement. In a previous study we have described a delayed withdrawal syndrome after successful motor improvement related to subthalamic stimulation allowing for a major decrease in dopaminergic treatment. This withdrawal syndrome correlated with a diffuse mesolimbic dopaminergic denervation. To confirm our hypothesis of parkinsonian apathy being related to mesolimbic dopaminergic denervation, we performed a randomized controlled study using piribedil, a relatively selective D2/D3 dopamine agonist to treat parkinsonian apathy, using the model of postoperative apathy. A 12-week prospective, placebo-controlled, randomized, double-blinded trial was conducted in 37 patients with Parkinson's disease presenting with apathy (Starkstein Apathy Scale score > 14) following subthalamic nucleus stimulation. Patients received either piribedil up to 300 mg per day (n = 19) or placebo (n = 18) for 12 weeks. The primary end point was the improvement of apathy under treatment, as assessed by the reduction of the Starkstein Apathy Scale score in both treatment groups. Secondary end points included alleviation in depression (Beck Depression Inventory), anxiety (Beck Anxiety Inventory), improvement of quality of life (PDQ39) and anhedonia (Snaith-Hamilton Pleasure Scale). Exploratory endpoints consisted in changes of the Robert Inventory score and Hamilton depression scales. An intention to treat analysis of covariance analysis was performed to compare treatment effects (P < 0.05). The number of premature study dropouts was seven in the placebo and five in the piribedil groups, mostly related to intolerance to hypodopaminergic symptoms. At follow-up evaluation, the apathy score was reduced by 34.6% on piribedil versus 3.2% on placebo (P = 0.015). With piribedil, modifications in the Beck depression and anxiety scores were -19.8% and -22.8%, respectively versus +1.4% and -8.3% with placebo, without reaching significance level. Piribedil led to a trend towards improvement in quality of life (-16.2% versus +6.7% on placebo; P = 0.08) and anhedonia (-49% versus -5.6% on the placebo; P = 0.08). Apathy, assessed by the Robert Inventory score, improved by 46.6% on piribedil and worsened by 2.3% on placebo (P = 0.005). Depression, measured by the Hamilton score, improved in the piribedil group (P = 0.05). No significant side effects were observed. The present study provides a class II evidence of the efficacy of the dopamine agonist piribedil in the treatment of apathy in Parkinson's disease.

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.

Background: Detecting patients at risk for secondary neurological deterioration (SND) after mild to moderate traumatic brain injury is challenging., Objective: To assess the diagnostic accuracy of transcranial Doppler (TCD) on admission in screening these patients., Methods: This prospective, observational cohort study enrolled 98 traumatic brain injury patients with an initial Glasgow Coma Scale score of 9 to 15 whose initial computed tomography (CT) scan showed either absent or mild lesions according to the Trauma Coma Data Bank (TCDB) classification, ie, TCDB I and TCDB II, respectively. TCD measurements of the 2 middle cerebral arteries were obtained on admission under stable conditions in all patients. Neurological outcome was reassessed on day 7., Results: Of the 98 patients, 21 showed SND, ie, a decrease of ≥ 2 points from the initial Glasgow Coma Scale or requiring any treatment for neurological deterioration. Diastolic cerebral blood flow velocities and pulsatility index measurements were different between patients with SND and patients with no SND. Using receiver-operating characteristic analysis, we found the best threshold limits to be 25 cm/s (sensitivity, 92%; specificity, 76%; area under curve, 0.93) for diastolic cerebral blood flow velocity and 1.25 (sensitivity, 90%; specificity, 91%; area under curve, 0.95) for pulsatility index. According to a recursive-partitioning analysis, TCDB classification and TCD measurements were the most discriminative among variables to detect patients at risk for SND., Conclusion: In patients with no severe brain lesions on CT after mild to moderate traumatic brain injury, TCD on admission, in complement with brain CT scan, could accurately screen patients at risk for SND., (Copyright © 2011 by the Congress of Neurological Surgeons)

Unlabelled: Brain-computer interfaces (BCIs) include stimulators, infusion devices, and neuroprostheses. They all belong to functional neurosurgery. Deep brain stimulators (DBS) are widely used for therapy and are in need of innovative evolutions. Robotized exoskeletons require BCIs able to drive up to 26 degrees of freedom (DoF). We report the nanomicrotechnology development of prototypes for new 3D DBS and for motor neuroprostheses. For this complex project, all compounds have been designed and are being tested. Experiments were performed in rats and primates for proof of concepts and development of the electroencephalogram (EEG) recognition algorithm., Methods: Various devices have been designed. (A) In human, a programmable multiplexer connecting five tetrapolar (20 contacts) electrodes to one DBS channel has been designed and implanted bilaterally into STN in two Parkinsonian patients. (B) A 50-mm diameter titanium implant, telepowered, including a radioset, emitting ECoG data recorded by a 64-electrode array using an application-specific integrated circuit, is being designed to be implanted in a 50-mm trephine opening. Data received by the radioreceiver are processed through an original wavelet-based Iterative N-way Partial Least Square algorithm (INPLS, CEA patent). Animals, implanted with ECoG recording electrodes, had to press a lever to obtain a reward. The brain signature associated to the lever press (LP) was detected online by ECoG processing using INPLS. This detection allowed triggering the food dispenser., Results: (A) The 3D multiplexer allowed tailoring the electrical field to the STN. The multiplication of the contacts affected the battery life and suggested different implantation schemes. (B) The components of the human implantable cortical BCI are being tested for reliability and toxicology to meet criteria for chronicle implantation in 2012. (C) In rats, the algorithm INPLS could detect the cortical signature with an accuracy of about 80% of LPs on the electrodes with the best correlation coefficient (located over the cerebellar cortex), 1% of the algorithm decisions were false positives. We aim to pilot effectors with DoF up to 3 in monkeys., Conclusion: We have designed multielectrodes wireless implants to open the way for BCI ECoG-driven effectors. These technologies are also used to develop new generations of brain stimulators, either cortical or for deep targets. This chapter is aimed at illustrating that BCIs are actually the daily background of DBS, that the evolution of the method involves a growing multiplicity of targets and indications, that new technologies make possible and simpler than before to design innovative solutions to improve DBS methodology, and that the coming out of BCI-driven neuroprostheses for compensation of motor and sensory deficits is a natural evolution of functional neurosurgery., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Object: The aim of this study was to study the effects of MR imaging on the electrical settings of deep brain stimulation (DBS) systems and their clinical consequences., Methods: The authors studied the effects of 1.5-T MR imaging on the electrical settings of implanted DBS systems, including 1 or more monopolar or quadripolar leads, extension leads, and single- or dual-channel implantable pulse generators (IPGs). The IPG was switched off during the procedure and the voltage was set to 0. The impedances were checked before and after MR imaging., Results: Five hundred seventy patients were treated with DBS for movement disorders and underwent brain MR imaging after lead implantation and before IPG implantation. None of the patients experienced any adverse events. Thirty-one of these patients underwent 61 additional MR imaging sessions after the entire DBS system had been implanted. The authors report neither local cutaneous nor neurological disorders during or after the MR imaging session. No change in the IPG settings occurred when the magnet reed switch function remained disabled during the procedure., Conclusions: This study demonstrates that 1.5-T MR imaging can be performed safely with continuous monitoring in patients with a DBS system. The ability to disable the magnet reed switch function of the IPG prevents any change in the electrical settings and thus any side effects. The increasing number of DBS indications and the widespread use of MR imaging indicates the need for defining safety guidelines for the use of MR imaging in patients with implanted neurostimulators.

To characterize peritumoral BOLD contrast disorders, 25 patients referred for resection of primary frontal or parietal neoplasms (low-grade glioma (LGG) (n=8); high-grade glioma (HGG) (n=7); meningioma (n=10)) without macroscopic tumoral infiltration of the primary sensorimotor cortex (SM1) were examined preoperatively using BOLD fMRI during simple motor tasks. Overall cerebral BOLD signal was estimated using vasoreactivity to carbogen inhalation. Using bolus of gadolinium, cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) were estimated. In a 1cm(3) region-of-interest centered on maximal T-value in SM1 contralateral to movements, interhemispheric asymmetry was evaluated using interhemispheric ratios for BOLD and perfusion parameters. During motor tasks contralateral to the tumor, ipsitumoral sensorimotor activations were decreased in HGG and meningiomas, correlated to the distance between the tumor and SM1. Whereas CBV was decreased in ipsitumoral SM1 for HGG, it remained normal in meningiomas. Changes in basal perfusion could not explain motor activation impairment in SM1. Decreased interhemispheric ratio of the BOLD response to carbogen was the best predictor to model the asymmetry of motor activation (R=0.51). Moreover, 94.9+/-4.9% of all motor activations overlapped significant BOLD response to carbogen inhalation., (Copyright (c) 2010 Elsevier Inc. All rights reserved.)

Background: Cerebral palsy (CP) with dystonia-choreoathetosis is a common cause of disability in children and in adults, and responds poorly to medical treatment. Bilateral pallidal deep brain stimulation (BP-DBS) of the globus pallidus internus (GPi) is an effective treatment for primary dystonia, but the effect of this reversible surgical procedure on dystonia-choreoathetosis CP, which is a subtype of secondary dystonia, is unknown. Our aim was to test the effectiveness of BP-DBS in adults with dystonia-choreoathetosis CP., Methods: We did a multicentre prospective pilot study of BP-DBS in 13 adults with dystonia-choreoathetosis CP who had no cognitive impairment, little spasticity, and only slight abnormalities of the basal ganglia on MRI. The primary endpoint was change in the severity of dystonia-choreoathetosis after 1 year of neurostimulation, as assessed with the Burke-Fahn-Marsden dystonia rating scale. The accuracy of surgical targeting to the GPi was assessed masked to the results of neurostimulation. Analysis was by intention to treat., Findings: The mean Burke-Fahn-Marsden dystonia rating scale movement score improved from 44.2 (SD 21.1) before surgery to 34.7 (21.9) at 1 year post-operatively (p=0.009; mean improvement 24.4 [21.1]%, 95% CI 11.6-37.1). Functional disability, pain, and mental health-related quality of life were significantly improved. There was no worsening of cognition or mood. Adverse events were related to stimulation (arrest of the stimulator in one patient, and an adjustment to the current intensity in four patients). The optimum therapeutic target was the posterolateroventral region of the GPi. Little improvement was seen when the neurostimulation diffused to adjacent structures (mainly to the globus pallidus externus [GPe])., Interpretation: Bilateral pallidal neurostimulation could be an effective treatment option for patients with dystonia-choreoathetosis CP. However, given the heterogeneity of motor outcomes and the small sample size, results should be interpreted with caution. The optimum placement of the leads seemed to be a crucial, but not exclusive, factor that could affect a good outcome., Funding: National PHRC; Cerebral Palsy Foundation: Fondation Motrice/APETREIMC; French INSERM Dystonia National Network; Medtronic.

Purpose: Pilocytic astrocytomas (PA) and hemangioblastomas (HB) can present the same morphological characteristics on conventional MRI sequences, most usually in the form of a cerebellar cystic mass with a mural nodule that strongly enhances on post-contrast T1 images. We discuss here the value of perfusion MRI in the differentiation of these two tumors, the diagnoses of which have already been histopathologically established., Method: Eleven patients with PA and eight with HB underwent first-pass perfusion MRI. The maximum relative cerebral blood volume (rCBV(max)), defined as the ratio between the CBV(max) in tumor tissue and the CBV in healthy, contralateral white matter, is considered to be indicative of the type of tumor., Results: The difference between the rCBV(max) of PA (rCBV(max)=1.19+/-0.71, range 0.6-3.27) compared with that of HB (rCBV(max)=9.37+/-2.37, range 5.38-13) was significant (P<0.001). The first-pass curve crossed the baseline, corresponding to vascular permeability problems in both PA and HB., Conclusion: The first-pass method of perfusion MRI is a quick and useful way to differentiate between PA and HB.

High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN-HFS) is the preferred surgical treatment for advanced Parkinson's disease. In the 15 years since its introduction into clinical practice, many studies have reported on its benefits, drawbacks, and insufficiencies. Despite limited evidence-based data, STN-HFS has been shown to be surgically safe, and improvements in dopaminergic drug-sensitive symptoms and reductions in subsequent drug dose and dyskinesias are well documented. However, the procedure is associated with adverse effects, mainly neurocognitive, and with side-effects created by spread of stimulation to surrounding structures, depending on the precise location of electrodes. Quality of life improves substantially, inducing sudden global changes in patients' lives, often requiring societal readaptation. STN-HFS is a powerful method that is currently unchallenged in the management of Parkinson's disease, but its long-term effects must be thoroughly assessed. Further improvements, through basic research and methodological innovations, should make it applicable to earlier stages of the disease and increase its availability to patients in developing countries.

Since the 1960s, deep brain stimulation and spinal cord stimulation at low frequency (30 Hz) have been used to treat intractable pain of various origins. For this purpose, specific hardware have been designed, including deep brain electrodes, extensions, and implantable programmable generators (IPGs). In the meantime, movement disorders, and particularly parkinsonian and essential tremors, were treated by electrolytic or mechanic lesions in various targets of the basal ganglia, particularly in the thalamus and in the internal pallidum. The advent in the 1960s of levodopa, as well as the side effects and complications of ablative surgery (e.g., thalamotomy and pallidotomy), has sent functional neurosurgery of movement disorders to oblivion. In 1987, the serendipitous discovery of the effect of high-frequency stimulation (HFS), mimicking lesions, allowed the revival of the surgery of movement disorders by stimulation of the thalamus, which treated tremors with limited morbidity, and adaptable and reversible results. The stability along time of these effects allowed extending it to new targets suggested by basic research in monkeys. The HFS of the subthalamic nucleus (STN) has profoundly challenged the practice of functional surgery as the effect on the triad of dopaminergic symptoms was very significant, allowing to decrease the drug dosage and therefore a decrease of their complications, the levodopa-induced dyskinesias. In the meantime, based on the results of previous basic research in various fields, HFS has been progressively extended to potentially treat epilepsy and, more recently, psychiatric disorders, such as obsessive-compulsive disorders, Gilles de la Tourette tics, and severe depression. Similarly, suggested by the observation of changes in PET scan, applications have been extended to cluster headaches by stimulation of the posterior hypothalamus and even more recently, to obesity and drug addiction. In the field of movement disorders, it has become clear that STN stimulation is not efficient on the nondopaminergic symptoms such as freezing of gait. Based on experimental data obtained in MPTP-treated parkinsonian monkeys, the pedunculopontine nucleus has been used as a new target, and as suggested by the animal research results, its use indeed improves walking and stability when stimulation is performed at low frequency (25 Hz). The concept of simultaneous stimulation of multiple targets eventually at low or high frequency, and that of several electrodes in one target, is being accepted to increase the efficiency. This leads to and is being facilitated by the development of new hardware (multiple-channel IPGs, specific electrodes, rechargeable batteries). Still additional efforts are needed at the level of the stimulation paradigm and in the waveform. The recent development of nanotechnologies allows the design of totally new systems expanding the field of deep brain stimulation. These new techniques will make it possible to not only inhibit or excite deep brain structures to alleviate abnormal symptoms but also open the field for the use of recording cortical activities to drive neuroprostheses through brain-computer interfaces. The new field of compensation of deficits will then become part of the field of functional neurosurgery.

A model is a simplified preparation that reproduces only the most critical features of a disease. To be considered as a validated animal model, such an experimental preparation must fulfill three criteria: isomorphism or similarities of the symptoms; predictivity or identical pharmacological reactivity; homology or etiological similarity. In epilepsy, the use of animal models helps our understanding of physiological and pathological networks involved in the genesis, maintenance, and propagation of seizures. The animal models of epilepsy are also useful in designing and testing new surgical therapeutical strategies, in particular using deconnection or neuromodulation in drug-resistant focal epilepsies. Here we describe three animal models of focal epilepsy, adapted to addressing experimental surgery issues. Kindling consists in the regular liminar stimulation of a given brain structure in the rodent to develop a focal discharge that is secondarily generalized. The local application of epileptogenic agents such as cobalt, iron, or penicillin leads to focal discharges that do not generalize in the rodent or the primate. It is a model of focal neocortical epilepsy without secondary generalization. The focal application of kainate, an excitotoxic glutamate agonist, in the dorsal hippocampus of the adult mouse results, after a latent period, in spontaneous and recurrent focal discharges, behavioral interictal troubles, drug resistance, and histological anomalies reminiscent of hippocampal sclerosis. This constitutes a model of mesial-temporal epilepsy. Better knowledge, in these models, of the neural networks generating, propagating, and/or controlling the seizures should make it possible to design innovative surgical approaches for the treatment of drug-resistant epilepsies.

We report here the results of the first survey on epilepsy surgery activity in France. Data from a questionnaire sent to 17 centers practicing epilepsy surgery were analyzed. All centers responded; however, all items were not completely documented. Over 50 years, more than 5000 patients have been operated on for drug-resistant epilepsy and more than 3000 patients underwent some invasive monitoring, most often SEEG. Currently, nearly 400 patients (including more than 100 children) are operated on yearly for epilepsy in France. Over a study period varying among centers (from two to 20 years; mean, 9.5 years), results from more than 2000 patients including one-third children were analyzed. Important differences between adults and children, respectively, were observed in terms of location (temporal: 72% versus 4.3%; frontal: 12% versus 28%; central: 2% versus 11%), etiology (hippocampal sclerosis: 41% versus 2%; tumors 20% versus 61%); and procedures (cortectomy: 50% versus 23%; lesionectomy: 8% versus 59%), although overall results were identical (seizure-free rates following temporal lobe surgery: 80.6% versus 79%; following extratemporal surgery: 65.9% versus 65%). In adults, the best results were observed following temporomesial (TM) resection associated with hippocampal sclerosis or other lesions (class I: 83% and 79%, respectively), temporal neocortical (TNC) lesional (82%), while resections for cryptogenic temporal resections were followed by 69% (TM) and 63% (TNC) class I outcome. Extratemporal lesional resections were associated with 71% class I outcome and cryptogenic 43%. In children, the best results were obtained in tumor-associated epilepsy regardless of location (class I: 80%). A surgical complication occurred in 8% after resective surgery - with only 2.5% permanent morbidity - and 4.3% after invasive monitoring (mostly hemorrhagic). Overall results obtained by epilepsy surgery centers were in the higher range of those reported in the literature, along with a low rate of major surgical complications. Growing interest for epilepsy surgery is clearly demonstrated in this survey and supports further development to better satisfy the population's needs, particularly children. Activity should be further evaluated, while existing epilepsy surgery centers as well as healthcare networks should be expanded.

Objective: This study investigates the feasibility, safety, and usefulness of depth electrodes stereotactically implanted within the insular cortex., Methods: Thirty patients with suspected insular involvement during epileptic seizure underwent presurgical stereotactic electroencephalographic recordings using 10 to 16 depth electrodes per patient. Among these, one or two electrodes were implanted via an oblique approach to widely sample the insular cortex., Results: Thirty-five insular electrodes were implanted in the 30 patients without morbidity. A total of 226 recording contacts (mean, 7.5 contacts/patient) explored the insular cortex. Stereotactic electroencephalographic recordings of seizures allowed the differentiation into groups: Group 1, 10 patients with no insular involvement; Group 2, 15 patients with secondary insular involvement; and Group 3, five patients with an initial insular involvement. In temporal epilepsy (n = 17), the insula was never involved at the seizure onset but was frequently involved during the seizures (11 out of 17). In frontotemporal or frontal epilepsy, the insula was involved at the onset of seizure in five out of 13 patients. All patients in Groups 1 and 2 underwent surgery, with a seizure-free outcome in 76.2% of patients. In Group 3, only two of the five patients underwent surgery, with a poor outcome. In temporal lobe epilepsy, surgical outcome tended to be better in Group 1 compared with Group 2 in this small series: results were good in 83.3% (Engel I) versus 72.7%., Conclusion: Insula can be safely explored with oblique electrodes. In temporal lobe epilepsy, insular involvement does not significantly modify the short-term postoperative outcome. Future larger studies are necessary to clarify the long-term prognostic value of insular spread.

MR and CT imaging techniques provide both morphological data and functional data. MR and recently CT perfusion have substantially modified the treatment of acute stroke. CT perfusion offers new opportunities to improve the management strategy in vasospasm after subarachnoid hemorrhage. Both are also helpful for the diagnosis of brain tumors and the assessment of treatment effects.

Restraining excitatory neurotransmission within a seizure focus provides a nondestructive treatment strategy for intractable neocortical epilepsy. Clostridial toxin light chain (LC) inhibits synaptic transmission by digesting a critical vesicle-docking protein, synaptobrevin, without directly altering neuronal health. This study tests the treatment efficacy of adenoviral vector delivered LC (AdLC) on a model of seizures in rats induced by motor cortex penicillin (PCN) injection. LC expression significantly reduced electroencephalogram (EEG) frequency, amplitude, duration, and latency compared to control groups injected with either an adenoviral vector bearing green fluorescent protein (AdGFP) or phosphate buffered solution (PBS). Correspondingly, LC gene expression improved behavioral manifestations including seizure severity and latency. There was no statistical difference in motor function before and after vector administration between treatment and control groups. Histological analysis revealed spatially discrete LC expression with corresponding synaptobrevin depletion in the cortex surrounding the injection site. Thus, vector-mediated LC gene delivery is capable of improving both the EEG and behavioral manifestations of PCN-induced focal neocortical seizures through synaptobrevin depletion.

Introduction: In a few years, magnetic resonance imaging (MRI) has evolved from a morphology-based examination to one that encompasses metabolism and function., State of Art: MRI is a well-established tool for the initial evaluation of brain tumors, but conventional MR sequences have some limitations. Conventional MRI is unable to distinguish high-grade glioma from metastasis and abscess, to define precisely the histopathological grade of gliomas, to determine exactly the limits of tumor extension, to characterize meningeal tumors. Differentiation of tumor recurrence from treatment-related changes may be difficult with standard MR imaging because the interpretation is essentially based on volume analysis., Perspectives: 1H Spectroscopy, diffusion and perfusion imaging become possible with the development of MR imagers and can be routinely performed in clinical settings. They give complementary information about tumor metabolism and vascularity and allow a better analysis of post-treatment modifications. Functional and metabolic explorations should be used to characterize brain tumors.

High-frequency stimulation (HFS) of neural structures has been used since 1997 as an alternative to lesions in functional neurosurgery of movement disorders, and more recently, it has been applied to the treatment of epilepsies, obsessive-compulsive disorders, cluster headaches, and has other applications in experimental models, particularly for obesity. Although their clinical efficacy is not questioned, and that the effects most of the time parallel those of ablative techniques, leading to the concept of functional inhibition, the intimate mechanisms by which HFS induces excitation within fiber bundles and seems to inhibit cellular nuclei is still strongly debated. Principally due to the observation of long-term clinical effects over a period up to 15 years, it is clear that the mechanism is not due to a progressive lesion, as at every moment the interruption of stimulation reverses totally the effects. There is no current proof that long-term HFS is able to reset neural networks, or to induce profound modifications of the functional organization or of the synaptic connectivity. To understand what is responsible for the immediate, reversible and adaptable effects of HFS, several mechanisms must be considered, which might be involved simultaneously or in sequence: i) Jamming of neural transmission through stimulated nuclei is one possibility, based on the principle that the regular imposed activity might drive the neurons to fire in a regular pattern, making it impossible to transmit more subtle messages, either normal or abnormal. Although it is difficult to prove this type of mechanism, it might account for the reports of increased activity following HFS in various structures. ii) Direct inhibition of spike initiation at the level of the membrane could be due to activation of inhibitory terminals, particularly gaba-ergic, or by a blockade of the voltage gated ion channels. iii) Recent data show that HFS decreases the production and release of low molecular weight proteic neurotransmitters, which could account for the functional inhibition while the efferent axon is still excited by the electrical stimulus. iv) Retrograde activation of upstream neuronal structures, as reported in the external pallidum during stimulation of STN, might be responsible of additional jamming-like effects due to collisions with descending spikes.

The present study demonstrates the application of the Unsupervised Spike Sorting algorithm (USS) to separation of multi-unit recordings and investigation of neuronal activity patterns in the subthalamic nucleus (STN). This nucleus is the main target for deep brain stimulation (DBS) in Parkinsonian patients. The USS comprises a fast unsupervised learning procedure and allows sorting of multiple single units, if any, out of a bioelectric signal. The algorithm was tested on a simulated signal with different levels of noise and with application of Time and Spatial Adaptation (TSA) algorithm for denoising. The results of the test showed a good quality of spike separation and allow its application to investigation of neuronal activity patterns in a medical application. One hundred twenty-four single channel multi-unit records from STN of 6 Parkinsonian patients were separated with USS into 492 single unit trains. Auto- and crosscorrellograms for each unit were analyzed in order to reveal oscillatory, bursting and synchronized activity patterns. We analyzed separately two brain hemispheres. For each hemisphere the percentage of units of each activity pattern were calculated. The results were compared for the first and the second operated hemispheres of each patient and in total.

Globus pallidus internus (GPi) deep brain stimulation (DBS) increasingly shows promising efficacy in the treatment of severe primary generalized dystonia. Functional imaging studies have shown previously that dystonia could be related to abnormal cortical activation during voluntary movement. In the present study, the effects of GPi DBS on regional cerebral blood flow (rCBF) during a motor task were studied in patients with primary generalized dystonia. rCBF was measured using H215O and PET in eight control subjects and six patients with dystonia treated with bilateral GPi DBS. Subjects were scanned at rest and while performing joystick movements. Dystonic patients were tested in two conditions: 'OFF' (stimulator bilaterally switched off) and 'ON' (unilateral stimulation). In the 'OFF' condition, compared with rest, motor activation of the most dystonic hand was associated with overactivity in the contralateral dorsolateral prefrontal cortex, gyrus frontalis medialis, superior frontal gyrus (area 10), frontoorbital cortex and thalamus. In the 'ON' condition, GPi DBS contralaterally to the most dystonic hand induced a decrease of the overactivation in the same areas, as well as the putamen. According to the present study, generalized dystonia is associated with prefrontal overactivation which can be reversed by effective GPi DBS.

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.

STN-HFS is well known to improve patients with IPD. Because off-period dystonia mimics focal or generalized dystonia of other causes, we proposed bilateral STN-HFS to some patients with generalized dystonia. The aim of this study was to compare the efficacy of STN stimulation on off-period dystonia and generalized dystonia. From a larger series of patients with IPD, we selected 22 patients based on the presence of severe preoperative off-period dystonia rated > or = 3 in least one limb on a severity score ranging from 0 to 4. Four patients with generalized dystonia (Hallervorden-Spatz disease, n = 3; primary, n = 1) underwent bilateral STN-HFS. Dystonia of the four limbs was rated on video recordings in all patients before surgery and 3 months after surgery. In IPD, bilateral STN stimulation reduced the severity of off-period dystonia by 70% on the four limbs (preoperative mean severity score = 2.03 +/- 1.49; postoperative mean severity score = 0.60 +/- 0.78). In contrast, bilateral STN-HFS had no effect on generalized dystonia (preoperative mean severity score = 3.25 +/- 0.77; postoperative mean severity score = 3.12 +/- 0.62). Despite clinical similarities between off-period dystonia in Parkinson's disease and generalized dystonia in certain cases, the effect of chronic bilateral STN-HFS differs. STN stimulation is highly effective in off-period dystonia of IPD, whereas it does not improve generalized dystonia. The pathophysiologic mechanisms underlying dystonia in these two disorders are still unknown. Assuming that the mechanism of action of STN-HFS is similar regardless of the cause of dystonia, our findings suggest that the STN is not similarly involved in off-period dystonia of IPD and others dystonias.

Deep brain stimulation (DBS) is a neurosurgical treatment of Parkinson's disease that is applied to three targets: the ventral intermediate nucleus of the thalamus (Vim), the globus pallidus internas (GPi) and the subthalamic nucleus (STN). Vim DBS mainly improves contralateral tremor and, therefore, is being supplanted by DBS of the two other targets, even in patients with tremor dominant disease. STN and GPi DBS improve off-motor phases and dyskinesias. There is little comparative data between these procedures. The magnitude of the motor improvement seems more constant with STN than GPi DBS. STN DBS allows a decrease in antiparkinsonian drug doses and consumes moderate current. These advantages of STN over GPi DBS are offset by the need for more intensive postoperative management. The DBS procedure has the unique advantage of reversibility and adjustability over time. Patients with young-onset Parkinson's disease suffering from levodopa-induced motor complications but still responding well to levodopa and who exhibit no behavioral, mood, or cognitive impairment benefit the most from STN DBS. Adverse effects more specific of the DBS procedure are infection, cutaneous erosion, and lead breaking or disconnection. Intracranial electrode implantation can induce a hematoma or contusion. Most authors agree that the benefit to risk ratio of DBS is favorable., (Copyright 2002 Movement Disorder Society)

Studying the clinical effects induced by electrical stimulation of the subthalamic nucleus (STN) area in a parkinsonian patient under local anesthesia is a mandatory step to determine the precise location of the final chronic electrode. Using multiple microelectrodes, preferably in a concentric parallel array allows a precise mapping of the STN region. The most reliable features to determine the suitable target are stimulation-induced dyskinesias and rigidity decrease at a low intensity without adverse effects or only at far higher intensities. New skills are needed to assess all stimulation-induced effects and interpret them in anatomo-functional terms., (Copyright 2002 Movement Disorder Society)

Chronic high frequency (130 Hz) stimulation (HFS) of the thalamic target Vim, first used in our group in 1987 as a treatment of tremor of various origins, has been used over the last ten years in 137 patients. Since 1993, this method has been extended to two other targets (subthalamic nucleus (STN): 137 patients and the medial pallidum (GPi): 12 patients), based on recent experimental data in rats and monkeys. STN appears to be a target of major interest, able to control the three cardinal symptoms and to allow the decrease or suppression of levodopa treatment, which then also suppresses levodopa induced dyskinesias. The stereotactic technique is based on the determination of the target using ventriculography, MRI and electrophysiology, with both microrecording of single neuron activity and microstimulation inducing therapeutic symptom suppression and side effects. Chronic electrodes are then placed bilaterally at the best physiologically defined location and then connected to implantable stimulators (either 2 Itrel II or the new double channel Kinetra), operated at 130-185 Hz, 60 ms pulse width, 2.5 to 3.5 volts. There was no operative mortality and permanent morbidity was observed in 3 patients. The mechanisms of action of HFS are not fully understood, but are definitely related to high frequency and are probably different depending on the target. Inhibition of cellular activity or of neural network functions could be induced, by jamming of a retroactive loop for tremor, or by shutdown of neurotransmitter release in STN. Mechanisms within an individual target are also probably different for tremor or for other symptom alleviation. All cardinal symptoms are alleviated from tremor to akinesia and rigidity. This strong improvement allows the decrease of the drug dosage to approximately 30% of the preoperative level, which suppresses the levodopa-induced dyskinesias. The off period dystonias are also suppressed as well as freezings and falls. The effects remain stable over more than 5 years and in the same period, the off stimulation-off medication UPDRS remains stable and does not increase at the usual rate The low rate of permanent complications, the minor side effects and their immediate reversibility, the possibility of bilateral implantation in one session and the long-term persistence of symptom relief are strong arguments which support chronic HFS of STN as the method of choice when a surgical procedure is indicated for the treatment of Parkinson's disease and even more when a bilateral procedure is necessary. Recent data show that STN stimulation could be useful in the treatment of dystonia as well as some forms of epilepsy. It is therefore possible that DBS in STN as well as in other targets could become a potent therapeutic tool in the near future for neurological disorders.

Deep brain stimulation by high frequency (HFS) has been developed starting in the thalamic target (Vim) from pragmatic observations and subsequently followed by other targets, such as the subthalamic nucleus (STN) and pallidum as an application of current knowledge from basic preclinical research in neuroscience. The mechanism involved by this neurosurgical approach is not completely solved. For Vim we have formed the hypothesis that HFS induces a jamming of sensory-motor loops but for the STN, from our experimental research in rats we have shown that HFS induces functional inhibition of cell activity in the target nuclei. In our patients the implantation of the stimulation electrodes was carried out stereotactically, under local anesthesia, using ventriculography, MRI, microrecordings and clinical evaluation of the effects of stimulation on rigidity. When the stimulation is turned ON in the STN area a significant decrease in rigidity was determined by the neurologists. Stimulation or even penetration of the electrode may be responsible for transient dyskinesias. The average location of the clinically efficient contact of the chronic stimulating electrodes is statistically located at 5.02 +/- 0.71 1/12 degrees of AC-PC in the AP direction, at -1.5 +/- 0.66 1/8 degrees of the height of the thalamus in the ventricle direction, with laterality at 11.98 +/- 1.12 mm in the lateral direction. The beneficial effects of STN stimulation are significant providing that the electrodes are correctly placed into the target. There is strong improvement of the symptoms of the triad in which akinesia, rigidity, and tremor are reduced on average to 41. 6, 48.6, and 27%, respectively, when compared with the previous preoperative level. From our experience, HFS of the STN could be considered the surgical therapy of choice at advanced stages of Parkinson's disease.