Publications by authors named "Patrick Mertens"

75 Publications

Comparison of clinical outcomes and accuracy of electrode placement between robot-assisted and conventional deep brain stimulation of the subthalamic nucleus: a single-center study.

Acta Neurochir (Wien) 2021 Mar 2. Epub 2021 Mar 2.

Service de Neurologie C, Centre Expert Parkinson, Hôpital Neurologique et Neurochirurgical Pierre Wertheimer, Hospices Civils de Lyon, 69003, Lyon, France.

Background: Several surgical methods are used for deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD). This study aimed to compare clinical outcomes and electrode placement accuracy after robot-assisted (RAS) versus frame-based stereotactic (FSS) STN DBS in Parkinson's disease.

Methods: In this single-center open-label study, we prospectively collected data from 48 consecutive PD patients who underwent RAS (Neuromate®; n = 20) or FSS (n = 28) STN DBS with the same MRI-based STN targeting between October 2016 and December 2018 in the university neurological hospital of Lyon, France. Clinical variables were assessed before and 1 year after surgery. The number of electrode contacts within the STN was determined by merging post-operative CT and pre-operative MRI using Brainlab® GUIDE™XT software.

Results: One year after surgery, the improvement of motor manifestations (p = 0.18), motor complications (p = 0.80), and quality of life (p= 0.30) and the reduction of dopaminergic treatment (p = 0.94) and the rate of complications (p = 0.99) were similar in the two groups. Surgery duration was longer in the RAS group (p = 0.0001). There was no difference in the number of electrode contacts within the STN.

Conclusion: This study demonstrates that RAS and FSS STN DBS for PD provide similar clinical outcomes and accuracy of electrode placement.
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http://dx.doi.org/10.1007/s00701-021-04790-7DOI Listing
March 2021

Microsurgical DREZotomy for Treatment of Brachial Plexus Avulsion Pain.

World Neurosurg 2021 Apr 28;148:177. Epub 2021 Jan 28.

Functional Neurosurgery Department, Neurology and Neurosurgery Hospital Pierre Wertheimer, Hospices Civils de Lyon, Lyon, France; University of Lyon, University Claude Bernard Lyon I, Lyon, France; Anatomy Laboratory, University of Lyon, Université Claude Bernard Lyon I, Lyon, France.

A 63-year-old man with a history of motorcycle accident 42 years ago suffered a left brachial plexus avulsion (BPA). Neuropathic pain in his left upper limb was felt in the C6-C7-C8 dermatomes. The rationale for performing "DREZotomy" is to preferentially interrupt the nociceptive inputs in the lateral part of the dorsal root entry zone (DREZ). For pain with complete deafferentation, as observed in BPA, the aim is to destroy the hyperactive nociceptive neurons deep in the apex of the dorsal horn (DH). Surgery is performed under general anesthesia, with the patient in prone position. Once the dura mater is opened, the arachnoid needs extensive dissection to open the dorsolateral and lateral spinal cisterns. In cases of BPA, the dorsolateral sulcus may be difficult to identify. Three anatomic elements can facilitate its recognition. Firstly, the remaining intact rootlets (above and below the avulsed segments) allow us to roughly localize the dorsolateral sulcus by joining these cranial and caudal normal rootlets. Secondly, blood vessels running on the spinal cord penetrate into the dorsolateral sulcus and often delineate the sulcus. Thirdly, scarring can be seen along the sulcus with small holes where the rootlets used to penetrate the cord. DREZotomy is performed using a graduated sharp bipolar instrument to allow precise microcoagulations of the DH. Preoperative surgical planning helps the surgeon by giving the angle between the DH and median plane. In the immediate postoperative period, the patient described the complete disappearance of neuropathic pain in his left upper limb, persistent at last follow-up (1 year) (Video 1).
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http://dx.doi.org/10.1016/j.wneu.2021.01.054DOI Listing
April 2021

Stimulation of the motor cerebral cortex in chronic neuropathic pain: the role of electrode localization over motor somatotopy.

J Neurosurg Sci 2020 Sep 18. Epub 2020 Sep 18.

Department of Neurosurgery, Pierre Wertheimer Hospital, Hospices Civils de Lyon, Lyon 1 University, Lyon, France.

Background: Previous studies have reported the pain-relieving effect of chronic electrical motor cortex stimulation (eMCS) in various types of neuropathic pain.

Objective: The study aimed to explore the potential relationship between the clinical efficacy of eMCS for the treatment of chronic neuropathic pain and the precise localization of the contacts over the motor cortex somatotopic representation of the painful area.

Methods: A total of 22 patients with neuropathic pain were implanted with eMCS electrodes. Implantation of the electrodes was performed using intraoperative 1) anatomical identification by neuronavigation software using 3D-MRI; 2) monitoring of somesthetic evoked potentials to check the potential reverse over the central sulcus; and 3) electrical stimulations through the dura to identify the motor responses and its somatotopy. Image fusion of postoperative 3D-CT and preoperative MRI images allowed postoperative location of the electrodes.

Results: Analgesic effects were obtained in 18 (81.81%) out of 22 patients. Postoperative 3D-CT analysis showed a correspondence between localization of the contacts and the motor cerebral cortex somatotopy in the patients with postoperative good analgesic effects. No correspondence was found between localization of the contacts and the motor cerebral cortex somatotopy in the four patients with no analgesic effects. In three out of these four patients, analgesic effects were obtained after new surgery allowed repositioning of the electrode over the motor cortex somatotopy of the painful area.

Conclusions: The findings of this study suggest that eMCS provides analgesic effects when the stimulated cortex corresponds to the somatotopy of the painful area.
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http://dx.doi.org/10.23736/S0390-5616.20.04991-7DOI Listing
September 2020

How Should we Use Multicolumn Spinal Cord Stimulation to Optimize Back Pain Spatial Neural Targeting? A Prospective, Multicenter, Randomized, Double-Blind, Controlled Trial (ESTIMET Study).

Neuromodulation 2021 Jan 31;24(1):86-101. Epub 2020 Aug 31.

Department of Neurosurgery, Spine & Neurostimulation Unit, Poitiers University Hospital, Poitiers, France.

Background: Recent studies have highlighted multicolumn spinal cord stimulation (SCS) efficacy, hypothesizing that optimized spatial neural targeting provided by new-generation SCS lead design or its multicolumn programming abilities could represent an opportunity to better address chronic back pain (BP).

Objective: To compare multicolumn vs. monocolumn programming on clinical outcomes of refractory postoperative chronic BP patients implanted with SCS using multicolumn surgical lead.

Materials And Methods: Twelve centers included 115 patients in a multicenter, randomized, double-blind, controlled trial. After randomization, leads were programmed using only one or several columns. The primary outcome was change in BP visual analogic scale (VAS) at six months. All patients were then programmed using the full potential of the lead up until 12-months follow-up.

Results: At six months, there was no significant difference in clinical outcomes whether the SCS was programmed using a mono or a multicolumn program. At 12 months, in all patients having been receiving multicolumn SCS for at least six months (n = 97), VAS decreases were significant for global pain (45.1%), leg pain (55.8%), and BP (41.5%) compared with baseline (p < 0.0001).

Conclusion: The ESTIMET study confirms the significant benefit experienced on chronic BP by patients implanted with multicolumn SCS, independently from multicolumn lead programming. These good clinical outcomes might result from the specific architecture of the multicolumn lead, giving the opportunity to select initially the best column on a multicolumn grid and to optimize neural targeting with low-energy requirements. However, involving more columns than one does not appear necessary, once initial spatial targeting of the "sweet spot" has been achieved. Our findings suggest that this spatial concept could also be transposed to cylindrical leads, which have drastically improved their capability to shape the electrical field, and might be combined with temporal resolution using SCS new modalities.
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http://dx.doi.org/10.1111/ner.13251DOI Listing
January 2021

How I do it: selective tibial neurotomy.

Acta Neurochir (Wien) 2020 08 7;162(8):1921-1923. Epub 2020 May 7.

Service de Neurochirurgie Fonctionnelle, Hospices Civils de Lyon, Hôpital neurologique et neurochirurgical Pierre Wertheimer, 59 Bd Pinel, 69003, Lyon, France.

Background: Selective neurotomy is known as an effective method to reduce focal spasticity when medical treatment including botulinum toxin is not sufficient. The tibial nerve can be targeted to treat spastic equinovarus foot with (or without) claw toes.

Method: Tibial nerve trunk is dissected in the popliteal fossa. Sensitive and motor branches are identified using electrical stimulation to monitor motor responses. The muscular nerves corresponding to the targeted muscles are partially sectioned according to a preoperative chart. A postoperative rehabilitation program is mandatory.

Conclusion: Precise and rigorous selective neurotomy provided a definitive and safe treatment for spastic equinovarus foot.
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http://dx.doi.org/10.1007/s00701-020-04314-9DOI Listing
August 2020

Overcoming challenges of the human spinal cord tractography for routine clinical use: a review.

Neuroradiology 2020 Sep 4;62(9):1079-1094. Epub 2020 May 4.

Laboratoire CREATIS, CNRS UMR5220, Inserm U1206, INSA-Lyon, Université de Lyon I, Lyon, France.

The spinal cord (SC) is a dense network of billions of fibers in a small volume surrounded by bones that makes tractography difficult to perform. We aim to provide a review collecting all technical settings of SC tractography and propose the optimal set of parameters to perform a good SC tractography rendering. The MEDLINE database was searched for articles reporting "spinal cord" "tractography" in "humans". Studies were selected only when tractography rendering was displayed and MRI acquisition and tracking parameters detailed. From each study, clinical context, imaging acquisition settings, fiber tracking parameters, region of interest (ROI) design, and quality of the tractography rendering were extracted. Quality of tractography rendering was evaluated by several objective criteria proposed herein. According to the reported studies, to obtain a good tractography rendering, diffusion tensor imaging acquisition should be performed with 1.5 or 3 Tesla MRI, in the axial plane, with > 20 directions; b value: 1000 s mm; right-left phase-encoding direction for cervical SC; isotropic voxel size; and no slice gap. Concerning the tracking process, it should be performed with determinist approach, fractional anisotropy threshold between 0.15 and 0.2, and curvature threshold of 40°. ROI design is an essential step for providing good tractography rendering, and their placement has to consider partial volume effects, magnetic susceptibility effects, and motion artifacts. The review reported herein highlights that successful SC tractography depends on many factors (imaging acquisition settings, fiber tracking parameters, and ROI design) to obtain a good SC tractography rendering.
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http://dx.doi.org/10.1007/s00234-020-02442-8DOI Listing
September 2020

Stereoscopic three-dimensional visualization: interest for neuroanatomy teaching in medical school.

Surg Radiol Anat 2020 Jun 29;42(6):719-727. Epub 2020 Feb 29.

Department of Anatomy, Faculté de médecine Lyon-Est, Université de Lyon, Université Claude Bernard Lyon I, 8 Avenue Rockefeller, 69003, Lyon, France.

Purpose: The anatomy of both the brain and the skull is particularly difficult to learn and to teach. Since their anatomical structures are numerous and gathered in a complex tridimensional (3D) architecture, classic schematical drawing or photography in two dimensions (2D) has difficulties in providing a clear, simple, and accurate message. Advances in photography and computer sciences have led to develop stereoscopic 3D visualization, firstly for entertainment then for education. In the present study, we report our experience of stereoscopic 3D lecture for neuroanatomy teaching to early medical school students.

Methods: High-resolution specific pictures were taken on various specimen dissections in the Anatomy Laboratory of the University of Lyon, France. Selected stereoscopic 3D views were displayed on a large dedicated screen using a doubled video projector. A 2-h stereoscopic neuroanatomy lecture was given by two neuroanatomists to third-year medicine students who wore passive 3D glasses. Setting up lasted 30 min and involved four people. The feedback from students was collected and analyzed.

Results: Among the 483 students who have attended the stereoscopic 3D lecture, 195 gave feedback, and all (100%) were satisfied. Among these, 190 (97.5%) reported a better knowledge transfer of brain anatomy and its 3D architecture. Furthermore, 167 (86.1%) students felt it could change their further clinical practice, 179 (91.8%) thought it could enhance their results in forthcoming anatomy examinations, and 150 (76.9%) believed such a 3D lecture might allow them to become better physicians. This 3D anatomy lecture was graded 8.9/10 a mean against 5.9/10 for previous classical 2D lectures.

Discussion-conclusion: The stereoscopic 3D teaching of neuroanatomy made medical students enthusiastic involving digital technologies. It could improve their anatomical knowledge and test scores, as well as their clinical competences. Depending on university means and the commitment of teachers, this new tool should be extended to other anatomical fields. However, its setting up requires resources from faculties and its impact on clinical competencies needs to be objectively assessed.
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http://dx.doi.org/10.1007/s00276-020-02442-6DOI Listing
June 2020

Anatomy of the human spinal cord arachnoid cisterns: applications for spinal cord surgery.

J Neurosurg Spine 2019 Jul 12:1-8. Epub 2019 Jul 12.

1Department of Neurosurgery, Hôpital Neurologique et Neurochirurgical Pierre Wertheimer, Hospices Civils de Lyon.

Objective: The goal in this study was to describe the overall organization of the spinal arachnoid mater and spinal subarachnoid space (SSAS) as well as its relationship with surrounding structures, in order to highlight spinal cord arachnoid cisterns.

Methods: Fifteen spinal cords were extracted from embalmed adult cadavers. The organization of the spinal cord arachnoid and SSAS was described via macroscopic observations, optical microscopic views, and scanning electron microscope (SEM) studies. Gelatin injections were also performed to study separated dorsal subarachnoid compartments.

Results: Compartmentalization of SSAS was studied on 3 levels of axial sections. On an axial section passing through the tips of the denticulate ligament anchored to the dura, 3 subarachnoid cisterns were observed: 2 dorsolateral and 1 ventral. On an axial section passing through dural exit/entrance of rootlets, 5 subarachnoid cisterns were observed: 2 dorsolateral, 2 lateral formed by dorsal and ventral rootlets, and 1 ventral. On an axial section passing between the two previous ones, only 1 subarachnoid cistern was observed around the spinal cord. This compartmentalization resulted in the anatomical description of 3 elements: the median dorsal septum, the arachnoid anchorage to the tip of the denticulate ligament, and the arachnoid anchorage to the dural exit/entrance of rootlets. The median dorsal septum already separated dorsal left and right subarachnoid spaces and was described from C1 level to 3 cm above the conus medullaris. This septum was anchored to the dorsal septal vein. No discontinuation was observed in the median dorsal arachnoid septum. At the entrance point of dorsal rootlets in the spinal cord, arachnoid trabeculations were described. Using the SEM, numerous arachnoid adhesions between the ventral surface of the dorsal rootlets and the pia mater over the spinal cord were observed. At the ventral part of the SSAS, no septum was found, but some arachnoid trabeculations between the arachnoid and the pia mater were present and more frequent than in the dorsal part. Laterally, arachnoid was firmly anchored to the denticulate ligaments' fixation at dural points, and dural exit/entrance of rootlets made a fibrous ring of arachnoidodural adhesions. At the level of the cauda equina, the arachnoid mater surrounded all rootlets together-as a sac and not individually.

Conclusions: Arachnoid cisterns are organized on each side of a median dorsal septum and compartmentalized in relation with the attachments of denticulate ligament and exit/entrance of rootlets.
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http://dx.doi.org/10.3171/2019.4.SPINE19404DOI Listing
July 2019

Ziconotide for spinal cord injury-related pain.

Eur J Pain 2019 10 29;23(9):1688-1700. Epub 2019 Aug 29.

Neurosurgical Department, Pierre Wertheimer Hospital, Hospices Civils de Lyon, Lyon 1 University, Lyon, France.

Background: Central neuropathic pain related to spinal cord injury is notoriously difficult to treat. So far most pharmacological and surgical options have shown but poor results. Recently ziconotide has been approved for use both neuropathic and non-neuropathic pain. In this cohort study, we assessed responder rate and long-term efficacy of intrathecal ziconotide in patients with pain related to spinal cord injury.

Methods: Patients presenting chronic neuropathic related to spinal cord lesions that was refractory to medical pain management were considered for inclusion. Those accepting were tested by lumbar puncture injection of ziconotide or continuous intrathecal infusion and if a significant decrease in pain scores (>40%) was noted they were implanted with a continuous infusion pump. They were then followed up for at least 1 year with constant assessment of the evolution of pain and side effects.

Results: Out of the 20 patients tested 14 had a decrease in pain scores of more than 40% but only 11 (55%) were implanted with permanent pumps due to side effects and patient choice. These were followed up on average for 3.59 years (±1.94) and in eight patients an above threshold decrease in pain scores was maintained. Overall in patients that responded to the test baseline VAS was 7.91 and 4.31 at last follow-up with an average dose of 7.2 μg of ziconotide per day. Six patients (30%) did not respond to any test and in three patients side effects precluded pump implantation. No significant long-term effects of the molecule were noted.

Conclusion: This study shows response to intrathecal ziconotide test in 40% of the patients of a very specific population in whom other therapeutic options are not available. This data justifies the development further studies such as a long-term randomized controlled trial.

Significance: Intrathecal Ziconotide is a posible alternative for the treatment of pain in patients with spinal cord injury and below level neuropathic pain.
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http://dx.doi.org/10.1002/ejp.1445DOI Listing
October 2019

Anatomical and Histological Analysis of a Complex Structure Too Long Considered a Simple Ligament: The Filum Terminale.

World Neurosurg 2019 Sep 29;129:e464-e471. Epub 2019 May 29.

Department of Neurosurgery, Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Bron, France; Faculty of Medicine Lyon Est, Claude Bernard University Lyon 1, Lyon, France; Laboratory of Anatomy, Faculty of Medicine Lyon Est, Claude Bernard University Lyon 1, Lyon, France.

Background: The intradural filum terminale (iFT) connects the conus medullaris (CM) with the dural sac (DS), and the extradural filum terminale (eFT) connects the DS to the coccyx. The aim of the present study was to update the description of the FT and integrate these data in a physiological and pathological context.

Methods: Anatomical measurements and histological investigations were performed on 10 human cadavers.

Results: The mean length of the iFT and eFT was 167.13 and 87.59 mm, respectively. The mean cranial diameter of the iFT was 1.84 mm. It was >2 mm in 2 specimens. The mean half and caudal diameter of the iFT was 0.71 and 0.74 mm, respectively. The cranial diameter of the eFT correlated with the caudal diameter of the eFT (ρ = 0.94; P = 0.02). The level of the CM-iFT junction correlated significantly with the iFT length (ρ = -0.67; P = 0.03). The mobilization of the iFT was not transmitted to the extradural elements and vice versa. The iFT contained axons and ependymal cells, which were dense in the first third and then randomly arranged caudally in islets. This could explain why ependymomas can occur all along the iFT. Ganglion cells were abundant around the junction with the DS. The eFT contained smooth muscle cells, adipocytes, and axons. A mechanoreceptor was identified in 1 specimen.

Conclusions: Consistently with their common embryological origin, a real anatomical and histological continuum is present between the CM and FT. The FT should, therefore, no longer be considered a simple ligament but, rather, a complex fibrocellular structure.
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http://dx.doi.org/10.1016/j.wneu.2019.05.184DOI Listing
September 2019

[Parkinson's disease: from the description of the disease to its surgical treatment].

Rev Prat 2018 May;68(5):574-578

Université de Lyon, institut des sciences cognitives Marc-Jeannerod, CNRS, UMR 5229, Bron, France.

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May 2018

Quality of life predicts outcome of deep brain stimulation in early Parkinson disease.

Neurology 2019 03 8;92(10):e1109-e1120. Epub 2019 Feb 8.

From the Département de Neurologie (W.M.M.S., A.H., T.D.H., F.P., Y.A., M.V.), Hôpital Pitié-Salpêtrière, Centre d'Investigation Clinique 1422, Institut du Cerveau et de la Moelle Epinière, Institut National de Santé et en Recherche Médicale, Assistance Publique Hôpitaux de Paris, France; Institute of Neurology (W.M.M.S.), Konolfingen; Department of Neurology (W.M.M.S.), University Hospital Bern and University of Bern, Switzerland; Medtronic (L.T.), Minneapolis, MN; Institute of Clinical Neuroscience & Medical Psychology and Department of Neurology (A.D., L.W.), Medical Faculty, Heinrich-Heine-University Düsseldorf, Germany; Movement Disorder Unit, Neurology (P.K.), CHU Grenoble Alpes; Grenoble Institut des Neurosciences (P.K., V.F., A. Kistner), University Grenoble Alpes; Inserm U1216 (P.K., V.F., A. Kistner), Grenoble, France; Department of Clinical Neurosciences (Neurology) (P.K.), Faculty of Medicine, University of Geneva, Switzerland; Coordinating Center for clinical trials of the Philipps University of Marburg (J.R., C.S.-B.); Neurochirurgische Klinik im Neurozentrum (A.F., L.P., S.P., J. Volkmann, K.K., G.D.),Christian-Albrechts-Universität Kiel; Neurologische Klinik und Poliklinik (J. Volkmann), Universitätsklinikum Würzburg; Department of Neurology (H.S.D., M.T.B., G.R.F., L.T.), University Hospital Cologne; Research Centre Jülich (G.R.F.); Klinik für Neurologie (T.D.H., A. Kühn, A. Kupsch) and Klinik für Neurochirurgie (G.-H.S.), Campus Virchow, Charité-Universitätsmedizin Berlin; Praxis Kupsch (A. Kupsch), Berlin, Germany; Service de Neurochirurgie (E.S.) and Service de Neurologie (V.F.), Hôpital Michallon, Centre Hospitalo-Universitaire, Grenoble; Departments of Neurosurgery (P.P.C.), Neurology (F.O.-M., C.B.-C.), and Clinical Pharmacology (C.B.-C.), University Hospital of Toulouse; ToNIC (F.O.-M., C.B.-C.), Toulouse Neuroimaging Center, University of Toulouse, Inserm, UPS, France; Department of Neurosurgery (J. Vesper), Universitätsklinikum Düsseldorf, Germany; Departments of Neurosurgery (S.D.) and Neurology (D.M.), Rouen University Hospital and University of Rouen; INSERM U1239 (D.M.), Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Mont-Saint-Aignan; Service de Neurologie (P. Damier, P. Derkinderen), CHU Nantes, Hôpital Laënnec, France; Paracelsus-Elena-Klinik Kassel (F.S.-D., C.T.); Department of Neurosurgery (C.T.), University Medical Center Göttingen; Division of Functional and Restorative Neurosurgery and Centre for Integrative Neuroscience (A.G.), Tübingen; Abteilung für Neurologie (T.W.), Reha-Zentrum Bad Gögging, Passauer Wolf; Department for Neurodegenerative Diseases and Hertie Institute for Clinical Brain Research (D.W.), University of Tübingen; Division of Stereotactic and Functional Neurosurgery (M.O.P.), University Medical Center Freiburg, Germany; Departments of Functional and Stereotactic Neurosurgery and Radiosurgery (J.-.M.R.) and Neurology (T.W.), Timone University Hospital, INSERM, Marseille; Institut des Sciences Cognitives Marc Jeannerod (S.T.), CNRS, UMR 5229, Université de Lyon; Centre Expert Parkinson (S.T.), Service de Neurologie C, Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron; Department of Neurosurgery (P.M.), University Hospital of Neurology and Neurosurgery, Hospices Civils de Lyon, Université de Lyon; Department of Neurology (J.-L.H.), INSERM-1402, Centre Hospitalier Universitaire de Poitiers, University of Poitiers, France; and Universitätsklinikum Giessen und Marburg (L.T.), Marburg Campus, Germany.

Objective: To investigate predictors for improvement of disease-specific quality of life (QOL) after deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson disease (PD) with early motor complications.

Methods: We performed a secondary analysis of data from the previously published EARLYSTIM study, a prospective randomized trial comparing STN-DBS (n = 124) to best medical treatment (n = 127) after 2 years follow-up with disease-specific QOL (39-item Parkinson's Disease Questionnaire summary index [PDQ-39-SI]) as the primary endpoint. Linear regression analyses of the baseline characteristics age, disease duration, duration of motor complications, and disease severity measured at baseline with the Unified Parkinson's Disease Rating Scale (UPDRS) (UPDRS-III "off" and "on" medications, UPDRS-IV) were conducted to determine predictors of change in PDQ-39-SI.

Results: PDQ-39-SI at baseline was correlated to the change in PDQ-39-SI after 24 months in both treatment groups ( < 0.05). The higher the baseline score (worse QOL) the larger the improvement in QOL after 24 months. No correlation was found for any of the other baseline characteristics analyzed in either treatment group.

Conclusion: Impaired QOL as subjectively evaluated by the patient is the most important predictor of benefit in patients with PD and early motor complications, fulfilling objective gold standard inclusion criteria for STN-DBS. Our results prompt systematically including evaluation of disease-specific QOL when selecting patients with PD for STN-DBS.

Clinicaltrialsgov Identifier: NCT00354133.
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http://dx.doi.org/10.1212/WNL.0000000000007037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442017PMC
March 2019

Understanding Anatomy of the Petrous Pyramid-A New Compartmental Approach.

World Neurosurg 2019 Jan 5. Epub 2019 Jan 5.

Department of Anatomy, University of Lyon 1, Lyon, France; Skull Base Multi-disciplinary Unit, Department of Neurosurgery B, Neurological Hospital Pierre Wertheimer, Hospices Civils de Lyon, Lyon Cedex, France.

Background: Learning surgical anatomy of the petrous pyramid can be a challenge, especially in the beginning of the training process. Providing an easier, holistic approach can be of help to everyone with interest in learning and teaching skull base anatomy. We present the complex organization of petrous pyramid anatomy using a new compartmental approach that is simple to understand and remember.

Methods: The surfaces of the petrous pyramid of two temporal bones were examined; and the contents of the petrous pyramid of 8 temporal bones were exposed through progressive drilling of the superior surface.

Results: The petrous pyramid is made up of a bony container, and its contents were grouped into 4 compartments (mucosal, cutaneous, neural, and vascular). Two reference lines were identified (mucosal and external-internal auditory canal lines) intersecting at the level of the middle ear. The localization of contents relative to these reference lines was then described, and 2 methods of segmentation (the X method and the V method) were then proposed. This description was then used to describe middle ear relationships, facial nerve anatomy, and air cell distribution.

Conclusions: This new compartmental approach allows a comprehensive understanding of the distribution of petrous pyramid contents. Dividing it into anatomic compartments, and then navigating this mental map along specific reference points, lines, spaces, and segments, could create a useful tool to teach or learn its complex tridimensional anatomy.
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http://dx.doi.org/10.1016/j.wneu.2018.11.234DOI Listing
January 2019

Spinal cord stimulation for chronic refractory pain: Long-term effectiveness and safety data from a multicentre registry.

Eur J Pain 2019 05 1;23(5):1031-1044. Epub 2019 Apr 1.

Département d'Anesthésie et Unité de Neuromodulation, Hôpital FOCH, Suresnes, France.

Background: Spinal cord stimulation (SCS) is an established therapy for refractory neuropathic pain. To ascertain the balance between treatment benefits and risks, the French National Authority for Health requested a post-market registry for real-world evaluation of the long-term effectiveness and safety of the therapy.

Methods: A total of 402 patients undergoing implantation with a Medtronic SCS device as either a primo-implant (n = 264) or replacement implant (n = 138) were enrolled across 28 representative sites in France. Outcome measures at 2 years included pain intensity, satisfaction with treatment, improvement of pain relief and daily life activity, willingness to undergo the treatment again and use of pain treatments. A patient was considered a responder if, compared to baseline, predominant pain reduction was ≥50%.

Results: At the 2-year follow-up visit, predominant pain intensity for primo-implant patients had decreased from baseline (p < 0.001), with responder rates of 55%, 36% and 67% for the lower limbs, back and upper limbs, respectively. Most patients acknowledged an improvement in pain relief (89%) and daily life activity (82%) were satisfied with treatment (91%) and willing to undergo the treatment again (93%). A significant decrease (p < 0.01) in the proportion of patients receiving pain treatment was observed for all drug and non-drug treatments. Reported adverse events were in line with the literature. Pain intensity at 2 years was comparable for patients in the replacement group, supporting the long-term stability and effectiveness of SCS.

Conclusion: Real-world evaluation of the use of spinal cord stimulation under the recommendations of the French Health Authority shows that two years after the first implantation of an SCS device close to 60% of the patients retain a significant pain reduction and 74% show improvement in pain scores [of at least 30%] with significant decreases in drug and non-drug pain treatments.

Significance: This observational, prospective study in a real-life setting followed a large cohort of patients suffering from chronic pain and implanted with SCS devices in France. The study assessed the long-term effectiveness and safety of SCS therapy in a representative sample of implanting sites in France.
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http://dx.doi.org/10.1002/ejp.1355DOI Listing
May 2019

Toe dystonia in Parkinson's disease: Impact of subthalamic nucleus deep brain stimulation.

J Neurol Sci 2018 09 12;392:65-68. Epub 2018 Jul 12.

Institut des Sciences Cognitives Marc Jeannerod, UMR 5229, CNRS, Bron, France; Service de Neurologie C, Centre Expert Parkinson, Hôpital Neurologique Pierre, Wertheimer, Hospices Civils de Lyon, Lyon, France; Faculté de médecine Lyon Sud Charles Mérieux, Université Lyon 1, Univ Lyon, Lyon, France.

Background: Off state toe dystonia (TD) is a symptom frequently encountered in Parkinson's disease (PD), but little is known about its evolution after subthalamic nucleus deep brain stimulation (STN-DBS).

Objective: To analyze the prevalence and the evolution of TD in PD patients candidate to STN-DBS.

Methods: Individual data of consecutive 130 PD patients who underwent STN-DBS between 2010 and 2015 were collected.

Results: Data were successfully collected in 95 patients. TD affect 45.3% of the patients in our cohort. TD was present in 32.7% of patients before surgery and was alleviated by STN-DBS in 48% of the cases. Motor improvement provided by STN-DBS, levodopa-equivalent treatment diminution after surgery, disease duration or age at the time of surgery were not predictive of TD evolution. A younger age at PD diagnosis was significantly associated with TD resolution.

Conclusion: STN-DBS is partially efficient for TD but its evolution seems independent of significant predictive factors.
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http://dx.doi.org/10.1016/j.jns.2018.07.004DOI Listing
September 2018

Subthalamic stimulation and neuropsychiatric symptoms in Parkinson's disease: results from a long-term follow-up cohort study.

J Neurol Neurosurg Psychiatry 2018 08 7;89(8):836-843. Epub 2018 Feb 7.

Movement Disorders Unit, Department of Psychiatry Neurology and Neurological Rehabilitation, CHU Grenoble Alpes, Grenoble, France.

Background: Reports on behavioural outcomes after subthalamic nucleus deep brain stimulation in Parkinson's disease are controversial and limited to short-term data. Long-term observation in a large cohort allows a better counselling and management.

Methods: To determine whether a long-term treatment with subthalamic stimulation induces or reduces impulse control behaviours, neuropsychiatric fluctuations and apathy, 69 patients treated with subthalamic stimulation are prospectively and retrospectively assessed using Ardouin Scale of Behavior in Parkinson's Disease before and after 3-10 years of stimulation.

Results: At a mean follow-up of 6 years, all impulse control disorders and dopaminergic addiction were significantly decreased, apart from eating behaviour and hypersexuality. Neuropsychiatric fluctuations also significantly improved (ON euphoria: 38% of the patients before surgery and 1% after surgery, P<0.01; OFF dysphoria: 39% of the patients before surgery and 10% after surgery, P<0.01). However, apathy increased (25% of the patients after surgery and 3% before, P<0.01). With the retrospective analysis, several transient episodes of depression, apathy, anxiety and impulse control disorders occurred.

Conclusions: Bilateral subthalamic nucleus stimulation was overall very effective in improving impulse control disorders and neuropsychiatric fluctuations in parkinsonian patients in the long term despite a counteracting frequent apathy. Transient episodes of impulse control disorders still occurred within the follow-up. These findings recommend a close follow-up in parkinsonian patients presenting with neuropsychiatric symptoms before deep brain stimulation surgery.

Clinical Trial Registration: NCT01705418;Post-results.
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http://dx.doi.org/10.1136/jnnp-2017-316373DOI Listing
August 2018

Personality, dopamine, and Parkinson's disease: Insights from subthalamic stimulation.

Mov Disord 2017 Aug 23;32(8):1191-1200. Epub 2017 Jun 23.

Movement Disorders Unit, Department of Psychiatry Neurology and Neurological Rehabilitation, CHU Grenoble Alpes, Grenoble, France.

Background: Subthalamic stimulation improves the motor and neuropsychiatric symptoms of Parkinson's disease. However, the impact of this treatment on impulse control and personality is the subject of heavy debate. The objective of this study was to investigate personality changes after subthalamic stimulation.

Methods: Using Cloninger's biosocial model, we assessed personality in 73 Parkinson's disease patients before and 12 months after subthalamic stimulation accompanied by a drastic reduction in dopaminergic medication. Changes in psychobehavioral symptoms were measured using a battery of validated clinical scales (apathy, depression, anxiety, hyperemotionality, mania, psychosis, punding, and impulse control behaviors).

Results: One year after surgery, the harm avoidance personality domain total score increased compared with the baseline (+2.8; 34 patients; P < 0.001), as did 3 of its 4 subdomains: anticipatory worry (+0.7; 10 patients; P = 0.005), shyness (+0.6; 7 patients; P = 0.03), and fatigability (+1.1; 10 patients; P = 0.0014). Evolution of the shyness personality trait correlated with the decrease in dopaminergic medication. Total scores in the other personality domains remained unchanged, except for extravagance, a subdomain of novelty seeking, and persistence, a subdomain of reward dependence, which both decreased following surgery (-0.3; 7 patients; and -0.6; 9 patients; P = 0.03 and P = 0.0019, respectively). Although apathy increased, other psychobehavioral symptoms, including impulse control behaviors and neuropsychiatric nonmotor fluctuations, improved. Depression and anhedonia remained stable. Scores in hypodopaminergia and neuropsychiatric nonmotor OFF correlated with harm avoidance. Scores in hyperdopaminergia and neuropsychiatric nonmotor ON correlated with novelty seeking.

Conclusions: When subthalamic stimulation is applied in Parkinson's disease, significant changes in personality traits are observed, which may be related to postoperative tapering of dopaminergic treatment. © 2017 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.27065DOI Listing
August 2017

The maxillary artery and its variants: an anatomical study with neurosurgical applications.

Acta Neurochir (Wien) 2017 04 13;159(4):655-664. Epub 2017 Feb 13.

CHU de Lyon-Hôpital Neurologique et Neurochirurgical Pierre Wertheimer, Lyon, France.

Background: The maxillary artery (MA) has gained attention in neurosurgery particularly in cerebral revascularization techniques, intracranial endonasal approaches and endovascular procedures.

Objectives: To describe and illustrate the anatomy of the MA and its neurosurgical importance in a detailed manner.

Methods: Six cadaveric heads (12 MAs) were injected with latex. The arteries and surrounding structures were dissected and studied using microsurgical techniques. The dimensions, course and branching patterns of the MA were recollected. In addition, 20 three-dimensional reconstruction CT head and neck angiograms (3D CTAs) of actual patients were correlated with the cadaveric findings.

Results: The MA can be divided in three segments: mandibular, pterygoid and pterygopalatine. Medial and lateral trunk variants regarding its course around the lateral pterygoid muscle can be found. The different branching patterns of the MA have a direct correlation with the course of its main trunk at the base of the skull. Branching and trunk variants on one side do not predict the findings on the contralateral side.

Conclusion: In this study the highly variable course, branching patterns and relations of the MA are illustrated and described in human cadaveric heads and 3D CTAs. MA 3D CTA with bone reconstruction can be useful preoperatively for the identification of the medial or lateral course variants of this artery, particularly its pterygoid segment, which should be taken into account when considering the MA as a donor vessel for an EC-IC bypass.
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http://dx.doi.org/10.1007/s00701-017-3092-5DOI Listing
April 2017

The 360 photography: a new anatomical insight of the sphenoid bone. Interest for anatomy teaching and skull base surgery.

Surg Radiol Anat 2017 Jan 2;39(1):17-22. Epub 2016 Jun 2.

Department of Anatomy, University of Lyon 1, 8 Avenue Rockefeller, 69003, Lyon, France.

Skull base architecture is tough to understand because of its 3D complex shape and its numerous foramen, reliefs or joints. It is especially true for the sphenoid bone whom central location hinged with most of skull base components is unique. Recently, technological progress has led to develop new pedagogical tools. This way, we bought a new real-time three-dimensional insight of the sphenoid bone that could be useful for the teacher, the student and the surgeon. High-definition photography was taken all around an isolated dry skull base bone prepared with Beauchêne's technique. Pictures were then computed to provide an overview with rotation and magnification on demand. From anterior, posterior, lateral or oblique views and from in out looks, anatomical landmarks and subtleties were described step by step. Thus, the sella turcica, the optic canal, the superior orbital fissure, the sphenoid sinus, the vidian canal, pterygoid plates and all foramen were clearly placed relative to the others at each face of the sphenoid bone. In addition to be the first report of the 360 Photography tool, perspectives are promising as the development of a real-time interactive tridimensional space featuring the sphenoid bone. It allows to turn around the sphenoid bone and to better understand its own special shape, numerous foramen, neurovascular contents and anatomical relationships. This new technological tool may further apply for surgical planning and mostly for strengthening a basic anatomical knowledge firstly introduced.
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http://dx.doi.org/10.1007/s00276-016-1702-1DOI Listing
January 2017

Long-term efficacy and tolerability of bilateral pallidal stimulation to treat tardive dyskinesia.

Neurology 2016 Feb 20;86(7):651-9. Epub 2016 Jan 20.

From the Centre d'Investigation Clinique, Department of Neurology (H.P.-C., T.R., P. Damier), Department of Medical Evaluation and Epidemiology (J.-M.N.), and Department of Neurosurgery (S.R.), CHU Nantes, INSERM; Hôpital Neurologique (S.T., C.L., P.M.), Hospices Civils de Lyon, Université de Lyon 1; Centre d'Investigation Clinique, Department of Neurology (C.B.-C., F.O.-M., O.R.), CHU Toulouse, INSERM; Departments of Psychiatry (I.C.) and Neurology (P. Derost, M.U.), CHU Clermont-Ferrand; Departments of Neurosurgery (E.C.) and Neurology (D.G., P.B.), Bordeaux CHU; and the Departments of Neurology (A.E., T.W.) and Neurosurgery (J.R.), Assistance Publique Hôpitaux de Marseille, France.

Objective: To confirm the efficacy and safety of deep brain stimulation (DBS) of the internal part of the globus pallidus in improving severe tardive dyskinesia (TD).

Methods: Nineteen patients with severe pharmacoresistant TD were included. All were assessed at baseline and at 3, 6 (main outcome measure), and 12 months, and in the long term (6-11 years) for 14 patients, after bilateral pallidal DBS, using motor scales (Extrapyramidal Symptoms Rating Scale [ESRS], Abnormal Involuntary Movement Scale [AIMS]), cognitive scales, and a psychiatric assessment. At 6 months, a double-blind ESRS evaluation was performed in the stimulation "on" and stimulation "off" conditions.

Results: At 6 months, all patients had a decrease of more than 40% on the ESRS. The efficacy of the procedure was confirmed by a double-blind evaluation. This improvement was maintained at 12 months (ESRS: decrease of 58% [21%-81%];

Aims: decrease of 50% [7%-77%]) and in the long term (ESRS: decrease of 60% [22%-90%];

Aims: decrease of 63% [14%-94%], n = 14). All the subscores of the ESRS (parkinsonism, dystonia, and chorea) and of the AIMS (facial, oral, extremities, and trunk movements) improved. Despite psychiatric comorbidities at baseline, cognitive and psychiatric tolerability of the procedure was excellent. No cognitive decline was observed and mood was improved in most of the patients.

Conclusions: Pallidal DBS procedure should be considered as a therapeutic option in disabling TD refractory to medical treatment.

Classification Of Evidence: This study provides Class II evidence that in patients with severe pharmacoresistant TD with implanted pallidal leads, the stimulation "on" condition significantly improved ESRS scores compared to the stimulation "off" condition.
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http://dx.doi.org/10.1212/WNL.0000000000002370DOI Listing
February 2016

Intraoperative Monitoring of Diaphragm Neural Pathways During Cervical Surgery by Electrical Stimulation and Recordings of Ventilator Waveforms: Physiological Bases and Pilot Study.

J Neurosurg Anesthesiol 2017 Jan;29(1):30-36

*1st Department of Neurosurgery ‡Department of Anesthesiology and Reanimation, Hôpital Neurologique "Pierre Wertheimer," University of Lyon1, Lyon, France †Intensive Care Unit, "Agios Panteleimon" General Hospital of Nikaia-Peiraeus, Peiraeus, Greece.

Background: Surgery on the cervical spine entails the risk of damaging the neural structures responsible for diaphragmatic innervation, namely (C3)-C4-(C5) roots. In some "difficult" cases, anatomic identification of these structures may be hard to achieve. Therefore, monitoring of the diaphragm through the ventilation waveforms displayed on the anesthesia machine can be of practical help. According to literature review, very few publications have reported such monitoring.

Methods: The present work aimed at investigating the feasibility and reliability of identifying cervical root(s) responsible for diaphragmatic innervation, by observing the changes on the recorded waveforms, indicating diaphragmatic responses to direct radicular electrical stimulation. In this study, the events not only on the capnography curve but also on pressure-time and flow-time waveforms were analyzed. Eight patients undergoing cervical Microsurgical DREZotomy (MDT) were enrolled in the study, as this surgical modality allows easy access to the C4 root, known to be prominent in diaphragmatic innervation. The technique did not require any harmful additional maneuver to the current anesthesia and surgical protocols.

Results: Stimulation resulted in specific patterns of changes in the 3 waveforms in all 8 patients and proved "easy" to interpret, provided that close cooperation exists between the anesthesiologist and the surgeon.

Conclusion: Intraoperative monitoring of the diaphragmatic responses to stimulation can be advocated in surgery at the cervical spine level, and also more widely in surgery in the supraclavicular region, when neural structures responsible for diaphragmatic function are at risk.
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http://dx.doi.org/10.1097/ANA.0000000000000253DOI Listing
January 2017

Assessment of vinyl polysiloxane as an innovative injection material for the anatomical study of vasculature.

Surg Radiol Anat 2016 Apr 13;38(3):353-8. Epub 2015 Oct 13.

Département Universitaire d'Anatomie Rockefeller, Université Lyon 1, Faculté de Médecine de Lyon Est, 8, avenue Rockefeller, 69008, Lyon, France.

There are numerous injection materials for the study of vasculature in anatomical specimens, each having its own advantages and disadvantages. Latex and resins are the most widely used injection materials but need several days to set. The development of new materials taking shorter time to polymerize might be very useful to improve anatomic specimen study conditions. The aim of the present study was to evaluate vinyl polysiloxane (VPS), a silicon material widely used for dental impressions with the advantage to set very rapidly, as an injection material. We assessed the preparation, use, diffusion and setting time of the product in different anatomical regions (central nervous system, external carotid/jugular, lower limb) to observe its behavior in variably sized vessels. Our results suggest that VPS might be of interest for the study of vessels in anatomical specimens. The main strengths of the product are represented by (1) simplicity of use, as it is a ready-to-use material, (2) very rapid polymerization, (3) availability in a range of viscosities making easier the exploration of small vessels, (4) its better elasticity compared to resins, (5) and finally its availability in a range of colors making it a material of choice for vascular system dissections including those with very small caliber vessels.
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http://dx.doi.org/10.1007/s00276-015-1568-7DOI Listing
April 2016

Postoperative apathy can neutralise benefits in quality of life after subthalamic stimulation for Parkinson's disease.

J Neurol Neurosurg Psychiatry 2016 Mar 30;87(3):311-8. Epub 2015 Apr 30.

Movement Disorders Unit, Department of Psychiatry and Neurology, CHU de Grenoble, Université de Grenoble Alpes, Grenoble, France INSERM, U386, Grenoble Institut de Neurosciences, Grenoble, France.

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) improves motor symptoms of Parkinson's disease, leading to improvement in health-related quality of life (HRQoL). However, an excessive decrease in dopaminergic medication can lead to a withdrawal syndrome with apathy as the predominant feature. The present study aims to assess the impact of postoperative apathy on HRQoL.

Methods: A cohort of 88 patients who underwent STN-DBS was divided into two groups, those who were apathetic at 1 year and those who were not, as measured by the Starkstein scale. HRQoL was assessed using the Parkinson's disease questionnaire 39 (PDQ-39) and was compared between the two groups. We also compared activities of daily living, motor improvement and motor complications (Unified Parkinson's Disease Rating Scale, UPDRS), depression and anxiety, as well as cognition and drug dosages. Baseline characteristics and postoperative complications were recorded.

Results: One year after surgery, 27.1% of patients suffered from apathy. While motor improvement was significant and equivalent in both the apathy (-40.4% of UPDRS motor score) and non-apathy groups (-48.6%), the PDQ-39 score did not improve in the apathy group (-5.5%; p=0.464), whereas it improved significantly (-36.7%; p≤0.001) in the non-apathy group. Change in apathy scores correlated significantly with change in HRQoL scores (r=0.278, p=0.009). Depression and anxiety scores remained unchanged from baseline in the apathy group (p=0.409, p=0.075), while they improved significantly in patients without apathy (p=0.006, p≤0.001). A significant correlation was found between changes in apathy and depression (r=0.594, p≤0.001).

Conclusions: The development of apathy after STN-DBS can cancel out the benefits of motor improvement in terms of HRQoL. Systematic evaluation and management of apathy occurring after subthalamic stimulation appears mandatory.
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http://dx.doi.org/10.1136/jnnp-2014-310189DOI Listing
March 2016

Development of the sensorimotor cortex in the human fetus: a morphological description.

Surg Radiol Anat 2015 Mar 28;37(2):153-60. Epub 2014 Jun 28.

Department of Anatomy, Lyon 1 University, 8 Avenue Rockefeller, 69003, Lyon, France,

Twenty-one human fetal brains from 13 to 28 gestational weeks were studied macroscopically to describe the morphological stages of sulcal and gyral development in the sensorimotor cortex. In particular, the morphological appearance of the pericentral lateral cortex (sensorimotor cortex) and opercula was noted, as well as the vascularization of these regions. The central cerebral sulci were the first macroscopical structures to be identified on the lateral surface of the human cerebral hemisphere. Four chronological stages of sensorimotor cortex development were defined: stage 1: appearance at 18-19 gestational weeks (GWs) of the inferior part of the central cerebral sulcus; stage 2: development of the pericentral lateral regions and the beginning of opercularization at 20-22 GWs; stage 3: development of parietal and temporal cortices and the covering of the postcentral insular region at 24-26 GWs; and finally stage 4: maturation of the central cerebral regions at 27-28 GWs. These observations indicate the concomitance in the initiation of maturation of the pericentral cerebral cortices.
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http://dx.doi.org/10.1007/s00276-014-1332-4DOI Listing
March 2015

Is Life better after motor cortex stimulation for pain control? Results at long-term and their prediction by preoperative rTMS.

Pain Physician 2014 Jan-Feb;17(1):53-62

Neurophysiology & Epilepsy Unit, Neurological Hospital P. Wertheimer, Hospices Civils de Lyon, France; Inserm U 1028, NeuroPain team, Neuroscience Research Center of Lyon (CRNL), Lyon-1 University, France.

Background: A positive effect of motor cortex stimulation (MCS) (defined as subjective estimations of pain relief ≥ 30%) has been reported in 55 - 64% of patients. Repetitive magnetic cortical stimulation (rTMS) is considered a predictor of MCS effect. These figures are, however, mostly based on subjective reports of pain intensity, and have not been confirmed in the long-term.

Objectives: This study assessed long-term pain relief (2 - 9 years) after epidural motor cortex stimulation and its pre-operative prediction by rTMS, using both intensity and Quality of Life (QoL) scales.

Study Design: Analysis of the long-term evolution of pain patients treated by epidural motor cortex stimulation, and predictive value of preoperative response to rTMS.

Setting: University Neurological Hospital Pain Center.

Methods:

Patients: Twenty patients suffering chronic pharmaco-resistant neuropathic pain.

Intervention: All patients received first randomized sham vs. active 20 Hz-rTMS, before being submitted to MCS surgery.

Measurement: Postoperative pain relief was evaluated at 6 months and then up to 9 years post-MCS (average 6.1 ± 2.6 y) using (i) pain numerical rating scores (NRS); (ii) a combined assessment (CPA) including NRS, drug intake, and subjective quality of life; and (iii) a short questionnaire (HowRu) exploring discomfort, distress, disability, and dependence.

Results: Pain scores were significantly reduced by active (but not sham) rTMS and by subsequent MCS. Ten out of 20 patients kept a long-term benefit from MCS, both on raw pain scores and on CPA. The CPA results were strictly comparable when obtained by the surgeon or by a third-party on telephonic survey (r = 0.9). CPA scores following rTMS and long-term MCS were significantly associated (Fisher P = 0.02), with 90% positive predictive value and 67% negative predictive value of preoperative rTMS over long-term MCS results. On the HowRu questionnaire, long-term MCS-related improvement concerned "discomfort" (physical pain) and "dependence" (autonomy for daily activities), whereas "disability" (work, home, and leisure activities) and "distress" (anxiety, stress, depression) did not significantly improve.

Limitations: Limited cohort of patients with inhomogeneous pain etiology. Subjectivity of the reported items by the patient after a variable and long delay after surgery. Predictive evaluation based on a single rTMS session compared to chronic MCS.

Conclusions: Half of the patients still retain a significant benefit after 2 - 9 years of continuous MCS, and this can be reasonably predicted by preoperative rTMS. Adding drug intake and QoL estimates to raw pain scores allows a more realistic assessment of long-term benefits and enhance the rTMS predictive value. The aims of this study and its design were approved by the local ethics committee (University Hospitals St Etienne and Lyon, France).
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September 2014

Motor cortex stimulation does not improve dystonia secondary to a focal basal ganglia lesion.

Neurology 2014 Jan 6;82(2):156-62. Epub 2013 Dec 6.

From the CHU Clermont-Ferrand, Neurology Department (I.R., P.D., F.D.), and Neurosurgery Department (J.J.L.), Clermont-Ferrand; Clermont Université (I.R., P.D., F.D.), Université d'Auvergne, Clermont-Ferrand; Movement Disorder Unit (M.A.K., P.P.), Department of Psychiatry and Neurology, CHU de Grenoble, Joseph Fourier University and INSERM, Grenoble Institut des Neurosciences, Grenoble; Hospices Civils de Lyon, Hopital Neurologique Pierre Wertheimer, Neurologie C (S.T., J.X., E.B.), and Neurochirurgie A (P.M.); Université de Lyon (S.T., E.B., P.M.), Faculte de Médecine Lyon Sud Charles Mérieux, Lyon; CHU Clermont-Ferrand (B.P.), Biostatistics Unit, DRCI, Clermont-Ferrand; Department of Neurology (M.V.), CRICM UPMC/INSERM UMR_S975 CNRS UMR7225, Brain and Spine Institute, ICM, Pierre Marie Curie Paris-6 University, Salpêtrière Hospital, Paris; Univ Bordeaux (P.B.), Institut des Maladies Neurodégénératives, UMR 5293 and Service d'Explorations Fonctionnelles du Système Nerveux, Centre Hospitalier Universitaire, Bordeaux; Université Paris Est Créteil (J.P.L.), EA 4391 and AP-HP, Hôpital Henri Mondor, Service de Physiologie, Explorations Fonctionnelles, Créteil; and CHU Grenoble (S.C.), Neurosurgery Department, Grenoble, France.

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.
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http://dx.doi.org/10.1212/WNL.0000000000000012DOI Listing
January 2014

What is the dorsal median sulcus of the spinal cord? Interest for surgical approach of intramedullary tumors.

Surg Radiol Anat 2014 May 31;36(4):345-51. Epub 2013 Aug 31.

Department of Neurosurgery, Hôpital Neurologique Pierre Wertheimer, 59 Bd Pinel, 69677, Bron, Cedex, France,

Purpose: For intramedullary tumor (IMT) surgery, a balance has to be found between aggressively resecting the tumor and respecting all the sensory and motor pathways. The most common surgical approach is through the dorsal median sulcus (DMS) of the spinal cord. However, the precise organization of the meningeal sheats in the DMS remains obscure in the otherwise well-described anatomy of the spinal cord. A better understanding of this architecture may be of benefit to IMT surgeon to spare the spinal cord.

Methods: Three spinal cords were studied. The organization of the spinal cord meninges in the DMS was described via macroscopic, microsurgical and optical microscopic views. A micro dissection of the DMS was also performed.

Results: No macroscopic morphological abnormalities were observed. With the operative magnifying lens, the dura was opened, the arachnoid was removed and the pia mater was cut to access the DMS. The histological study showed that the DMS was composed of a thin rim of capillary-carrying connective tissue extending from the pia mater and covering the entire DMS. There was no true space between the dorsal columns, no arachnoid or crossing axons either.

Conclusion: Our work indicates that the DMS is not a sulcus but a thin blade of collagen extending from the pia mater. Its location is given by tiny vessels coming from the surface towards the deep. Thus, the surgical corridor has to follow the DMS as closely as possible to prevent damage to the spinal cord during midline IMT removal.
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http://dx.doi.org/10.1007/s00276-013-1194-1DOI Listing
May 2014

Brain opioid receptor density predicts motor cortex stimulation efficacy for chronic pain.

Pain 2013 Nov 27;154(11):2563-2568. Epub 2013 Jul 27.

Central Integration of Pain, Lyon Neuroscience Research Center, Lyon, France Laboratory of Neurosciences, St. Joseph University, Beirut, Lebanon Department of Functional Neurosurgery, Hôpital Neurologique, Lyon, France Department of Neurology and Pain center, Hôpital Nord, St-Etienne, France CERMEP Imagerie du vivant, Lyon, France Department of Anatomy, Claude Bernard University, Lyon, France.

The clinical effects of motor cortex stimulation (MCS) for neuropathic pain (NP) is thought to be mediated primarily by the secretion of endogenous opioids in humans and in animal models. Because opioid receptor density is itself decreased in patients with NP, we investigated whether the magnitude and distribution of the remaining opioid receptors in patients with NP could be biological predictors of the pain-relieving effects of MCS. Using (11)C-diprenorphine positron emission tomography scans, opioid receptor availability was assessed in 15 patients suffering refractory NP, who subsequently received chronically implanted MCS. All patients underwent 2 preoperative baseline scans at 2-wk intervals and were clinically assessed after 7mo of chronic MCS. The levels of preoperative opioid-binding in the insula, thalamus, periaqueductal gray, anterior cingulate, and orbitofrontal cortex were significantly and positively correlated with postoperative pain relief at 7mo. Patients with receptor density values below the lower limits in age-matched controls in the thalamus, periaqueductal gray and contralateral insula were the least likely to benefit from MCS. Opioid-receptor availability as shown in preoperative positron emission tomography scans appears to be related to the efficacy of MCS in NP and may help clinicians to select the candidates most likely to benefit from this procedure.
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http://dx.doi.org/10.1016/j.pain.2013.07.042DOI Listing
November 2013

Parkinsonian apathy responds to dopaminergic stimulation of D2/D3 receptors with piribedil.

Brain 2013 May 29;136(Pt 5):1568-77. Epub 2013 Mar 29.

Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Neurologie C 59 Bd Pinel, 69677 Bron, France.

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.
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http://dx.doi.org/10.1093/brain/awt067DOI Listing
May 2013

Is the medicolegal issue avoidable in neurosurgery? A retrospective survey of a series of 115 medicolegal cases from public hospitals.

World Neurosurg 2014 Feb 10;81(2):218-22. Epub 2013 Jan 10.

Service de Neurochirurgie, Hôpital Neurologique P. Wertheimer, Hospices Civils de Lyon, Faculté de Médecine, Université Lyon 1, Lyon, France.

Objective: Since the mid-1950s, neurosurgery has benefited from the remarkable progress due to tremendous advances in neuroimaging techniques, neuroanesthesia, neurostimulation, and brain-computer interfaces, as well as breakthroughs in operating microscopes and surgical instruments. Yet, this specialty has to do with delicate human structures and is hence considered as highly risky by insurance companies. In France, although neurosurgery's casualty rate (6%) is lower than in other specialties, the number of legal prosecutions has increased since 2002 because of easier access to medicolegal procedures. In order to avoid patients' resorting to the law courts, it becomes necessary to clearly identify the risk factors.

Methods: From the data bank of the insurer Société Hospitalière d'Assurances Mutuelles (SHAM, main insurance company for public hospitals in France), we retrospectively analyzed 115 files (34 cranial and 81 spinal surgeries) covering the period 1997-2007 for the reasons for complaints against French neurosurgeons working in public hospitals.

Results: Five main causes were identified: surgical site infection (37%), technical error (22%), lack of information (14%), delayed diagnosis (11%), and lack of supervision (9%).

Conclusion: Some causes are definitely avoidable at no cost to the hospital. Besides basic preventive safety procedures, we reiterate the mandatory steps for a good defense when being prosecuted. The evolution of patients' attitudes toward medical institutions observed in most countries has forced surgeons to adapt their practice. In this context, a common action certified by learned societies on sustainable health care quality, patient safety, and respect of good practices appears as the golden path to maintain a favorable legal, insurance, and financial environment.
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http://dx.doi.org/10.1016/j.wneu.2013.01.029DOI Listing
February 2014