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1.
J Neurooncol ; 157(1): 109-119, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35083580

ABSTRACT

PURPOSE: Targeted treatment for brainstem lesions requires above all a precise histopathological and molecular diagnosis. In the current technological era, robot-assisted stereotactic biopsies represent an accurate and safe procedure for tissue diagnosis. We present our center's experience in frameless robot-assisted biopsies for brainstem lesions. METHODS: We performed a retrospective analysis of all patients benefitting from a frameless robot-guided stereotactic biopsy at our University Hospital, from 2001 to 2017. Patients consented to the use of data and/or images. The NeuroMate® robot (Renishaw™, UK) was used. We report on lesion location, trajectory strategy, histopathological diagnosis and procedure safety. RESULTS: Our series encompasses 96 patients (103 biopsies) treated during a 17 years period. Mean age at biopsy: 34.0 years (range 1-78). Most common location: pons (62.1%). Transcerebellar approach: 61 procedures (59.2%). Most common diagnoses: diffuse glioma (67.0%), metastases (7.8%) and lymphoma (6.8%). Non conclusive diagnosis: 10 cases (9.7%). After second biopsy this decreased to 4 cases (4.1%). Overall biopsy diagnostic yield: 95.8%. Permanent disability was recorded in 3 patients (2.9%, all adults), while transient complications in 17 patients (17.7%). Four cases of intra-tumoral hematoma were recorded (one case with rapid decline and fatal issue). Adjuvant targeted treatment was performed in 72.9% of patients. Mean follow-up (in the Neurosurgery Department): 2.2 years. CONCLUSION: Frameless robot-assisted stereotactic biopsies can provide the initial platform towards a safe and accurate management for brainstem lesions, offering a high diagnostic yield with low permanent morbidity.


Subject(s)
Brain Neoplasms , Robotics , Adolescent , Adult , Aged , Biopsy/methods , Brain Neoplasms/pathology , Brain Stem/pathology , Child , Child, Preschool , Humans , Infant , Middle Aged , Retrospective Studies , Stereotaxic Techniques , Young Adult
2.
Neuromodulation ; 24(1): 86-101, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32865344

ABSTRACT

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.


Subject(s)
Failed Back Surgery Syndrome , Spinal Cord Stimulation , Back Pain/therapy , Humans , Pain Measurement , Prospective Studies , Spinal Cord , Treatment Outcome
3.
Cephalalgia ; 37(12): 1173-1179, 2017 Oct.
Article in English | MEDLINE | ID: mdl-27697849

ABSTRACT

Background Occipital nerve stimulation (ONS) has been proposed to treat chronic medically-intractable cluster headache (iCCH) in small series of cases without evaluation of its functional and emotional impacts. Methods We report the multidimensional outcome of a large observational study of iCCH patients, treated by ONS within a nationwide multidisciplinary network ( https://clinicaltrials.gov NCT01842763), with a one-year follow-up. Prospective evaluation was performed before surgery, then three and 12 months after. Results One year after ONS, the attack frequency per week was decreased >30% in 64% and >50% in 59% of the 44 patients. Mean (Standard Deviation) weekly attack frequency decreased from 21.5 (16.3) to 10.7 (13.8) ( p = 0.0002). About 70% of the patients responded to ONS, 47.8% being excellent responders. Prophylactic treatments could be decreased in 40% of patients. Functional (HIT-6 and MIDAS scales) and emotional (HAD scale) impacts were significantly improved, as well as the health-related quality of life (EQ-5D). The mean (SD) EQ-5D visual analogic scale score increased from 35.2 (23.6) to 51.9 (25.7) ( p = 0.0037). Surgical minor complications were observed in 33% of the patients. Conclusion ONS significantly reduced the attack frequency per week, as well as the functional and emotional headache impacts in iCCH patients, and dramatically improved the health-related quality of life of responders.


Subject(s)
Cluster Headache/therapy , Electric Stimulation Therapy/methods , Adult , Aged , Electric Stimulation Therapy/adverse effects , Female , Humans , Male , Middle Aged , Prospective Studies , Quality of Life , Treatment Outcome , Young Adult
4.
Stereotact Funct Neurosurg ; 94(6): 397-403, 2016.
Article in English | MEDLINE | ID: mdl-27992870

ABSTRACT

BACKGROUND/AIMS: Our study aimed to evaluate the efficiency and morbidity of Gamma Knife radiosurgery (GKS) in the treatment of hemorrhagic brainstem cavernous malformations (CMs). METHODS: We included in this study all patients who underwent GKS for the treatment of a hemorrhagic brainstem CM(s) in our institution between January 2007 and December 2012. The GKS was privileged when the surgical procedure was evaluated as very risky. The mean dose of radiation was 14.8 Gy, and the mean target volume was 0.282 cm3. All patients participated in a scheduled clinical follow-up. The posttreatment MRI was performed after 6 months and after 1 year, and then all patients had an annual MRI follow-up. RESULTS: There were 19 patients with a mean age of 36.7 years. The mean follow-up period was 51.2 months. The annual hemorrhage rate (AHR) was 27.31% before GKS, 2.46% during the first 2 years following the GKS, and 2.46% after the first 2 years following the GKS. The decrease in AHR after GKS was significant (p < 0.001). CONCLUSION: GKS should be suggested when the surgical procedure harbors a high risk of neurological morbidity in patients with brainstem CM. Compared to prior literature results, a lower dose than applied in this study could be discussed.


Subject(s)
Brain Stem/surgery , Cerebral Hemorrhage/surgery , Hemangioma, Cavernous, Central Nervous System/surgery , Radiosurgery/methods , Adult , Brain Stem/diagnostic imaging , Cerebral Hemorrhage/complications , Cerebral Hemorrhage/diagnostic imaging , Female , Follow-Up Studies , Hemangioma, Cavernous, Central Nervous System/complications , Hemangioma, Cavernous, Central Nervous System/diagnostic imaging , Humans , Male , Middle Aged , Young Adult
5.
Neuroimage ; 59(1): 168-80, 2012 Jan 02.
Article in English | MEDLINE | ID: mdl-21777680

ABSTRACT

Gaining new insights into the anatomy of the human hypothalamus is crucial for the development of new treatment strategies involving functional stereotactic neurosurgery. Here, using anatomical comparisons between histology and magnetic resonance images of the human hypothalamus in the coronal plane, we show that discrete gray and white hypothalamic structures are consistently identifiable by MRI. Macroscopic and microscopic images were used to precisely annotate the MRI sequences realized in the coronal plane in twenty healthy volunteers. MRI was performed on a 1.5 T scanner, using a protocol including T1-weighted 3D fast field echo, T1-weighted inversion-recovery, turbo spin echo and T2-weighted 2D fast field echo imaging. For each gray matter structure as well as for white matter bundles, the different MRI sequences were analyzed in comparison to each other. The anterior commissure and the fornix were often identifiable, while the mammillothalamic tract was more difficult to spot. Qualitative analyses showed that MRI could also highlight finer structures such as the paraventricular nucleus, the ventromedial nucleus of the hypothalamus and the infundibular (arcuate) nucleus, brain nuclei that play key roles in the regulation of food intake and energy homeostasis. The posterior hypothalamic area, a target for deep brain stimulation in the treatment of cluster headaches, was readily identified, as was the lateral hypothalamic area, which similar to the aforementioned hypothalamic nuclei, could be a putative target for deep brain stimulation in the treatment of obesity. Finally, each of the identified structures was mapped to Montreal Neurological Institute (MNI) space.


Subject(s)
Anatomy, Artistic , Atlases as Topic , Brain Mapping , Hypothalamus/anatomy & histology , Female , Humans , Magnetic Resonance Imaging , Male , Young Adult
6.
Stereotact Funct Neurosurg ; 90(2): 79-83, 2012.
Article in English | MEDLINE | ID: mdl-22286495

ABSTRACT

BACKGROUND: An important aspect of evaluating patients submitted to stereotactic biopsy of the brainstem is the trajectory used. The literature describes two principal approaches: the suboccipital transcerebellar and the transfrontal; however, no studies exist comparing these two techniques. OBJECTIVE: The purpose of this study was to compare diagnosis success rates and complications between the suboccipital transcerebellar and transfrontal trajectories. METHODS: The study evaluated 142 patients submitted to stereotactic biopsy. The patients presented brainstem tumors in the following areas: pons (n = 31), midbrain (n = 36), medulla (n = 2), pons-medulla (n = 30), pons-midbrain (n = 33), and midbrain-pons-medulla (n = 10). On 123 patients, the transfrontal approach was used, and on 19 the suboccipital transcerebellar approach. RESULTS: Comparing success rates between the two approaches, it was observed that in the group of patients submitted to the transfrontal approach, 95.1% (117 cases) were successful, while in those submitted to the suboccipital transcerebellar approach, 84.2% (16 cases) were successful. Despite a higher success rate among patients in the first group, the difference was not statistically significant. Regarding complications, in patients who were biopsied via the transfrontal trajectory, the morbidity rate was 9.8% (12 cases), while in patients submitted to the suboccipital transcerebellar approach, the morbidity rate was 5.3% (1 case) and the mortality rate 5.3% (1 case). CONCLUSIONS: This study verified a higher diagnosis rate in patients submitted to the transfrontal approach than in those submitted to the suboccipital transcerebellar approach (95.1 vs. 84.2%); however, the difference was not statistically significant. Regarding complications, the rate was similar in both groups of patients.


Subject(s)
Brain Stem Neoplasms/pathology , Brain Stem/pathology , Cerebellar Cortex , Stereotaxic Techniques , Adult , Biopsy/methods , Female , Humans , Male
7.
Brain ; 133(Pt 4): 1214-23, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20237130

ABSTRACT

Deep brain stimulation of the posterior hypothalamus is a therapeutic approach to the treatment of refractory chronic cluster headache, but the precise anatomical location of the electrode contacts has not been clearly assessed. Our aim was to study the location of the contacts used for chronic stimulation, projecting each contact centre on anatomic atlases. Electrodes were implanted in a series of 10 patients (prospective controlled trial) in the so-called 'posteroinferior hypothalamus' according to previously described coordinates, i.e. 2 mm lateral, 3 mm posterior and 5 mm below the mid-commissural point. The coordinates of the centre of each stimulating contact were measured on postoperative computed tomography or magnetic resonance imaging scans, taking into account the artefact of the electrode. Each contact centre (n=10; left and right hemispheres pooled) was displayed on the Schaltenbrand atlas and a stereotactic three dimensional magnetic resonance imaging atlas (4.7 tesla) of the diencephalon-mesencephalic junction for accurate anatomical location. Of the 10 patients with 1-year follow-up, 5 responded to deep brain stimulation (weekly frequency of attacks decrease >50%). In responders, the mean (standard deviation) coordinates of the contacts were 2.98 (1.16) mm lateral, 3.53 (1.97) mm posterior and 3.31 (1.97) mm below the mid-commissural point. All the effective contacts were located posterior to the hypothalamus. In responders, structures located <2 mm from the centres of effective contacts were: the mesencephalic grey substance (5/5), the red nucleus (4/5), the fascicle retroflexus (4/5), the fascicle longitudinal dorsal (3/5), the nucleus of ansa lenticularis (3/5), the fascicle longitudinal medial (1/5) and the thalamus superficialis medial (1/5). The contact coordinates (Wilcoxon test) and the structures (Fisher's exact test) were not significantly different between responders and non-responders. These findings suggest that failure of deep brain stimulation treatment in cluster headache may be due to factors unrelated to electrode misplacement. They also suggest that the therapeutic effect is probably not related to direct hypothalamic stimulation. Deep brain stimulation might modulate either a local cluster headache generator, located in the hypothalamus or in the mesencephalic grey substance, or non-specific anti-nocioceptive systems.


Subject(s)
Brain/anatomy & histology , Cluster Headache/pathology , Cluster Headache/therapy , Deep Brain Stimulation/instrumentation , Deep Brain Stimulation/methods , Adolescent , Adult , Aged , Electrodes, Implanted , Follow-Up Studies , Humans , Middle Aged , Prospective Studies , Young Adult
8.
Acta Neurochir (Wien) ; 153(5): 1111-21; discussion 1121-2, 2011 May.
Article in English | MEDLINE | ID: mdl-21331478

ABSTRACT

OBJECTIVE: Recent improvements in imaging-based diagnosis, the broader application of neuroendoscopic techniques and advances in open surgery techniques mean that the need for stereotactic biopsies in the management of pineal region tumours must be reevaluated. The primary aim of this retrospective study was to establish whether stereotactic biopsy is still of value in the modern management of pineal region tumours. METHODS: From 1985 to 2009, 88 consecutive patients underwent a stereotactic biopsy in our institution (51 males and 37 females; median age at presentation 30; range 2-74). RESULTS: Accurate tissue diagnoses were obtained in all but one case (i.e. 99%). In one case (1%), three distinct stereotactic procedures were necessary to obtain a tissue diagnosis. There was no mortality or permanent morbidity associated with stereotactic biopsy. One patient (1%) presented an intra-parenchymal hematoma but no related clinical symptoms. Five patients (6%) presented transient morbidity, which lasted for between 2 days and 3 weeks after the biopsy. CONCLUSIONS: To guide subsequent treatment, we believe that histological diagnosis is paramount. Stereotactic biopsies are currently the safest and the most efficient way of obtaining this essential information. Recent improvements in stereotactic technology (particularly robotic techniques) appear to be very valuable, with almost no permanent morbidity or mortality risk and no decrease in the accuracy rate. In our opinion, other available neurosurgical techniques (such as endoscopic neurosurgery, stereotactic neurosurgery and open microsurgery) are complementary and not competitive.


Subject(s)
Pinealoma/pathology , Pinealoma/surgery , Stereotaxic Techniques/standards , Adolescent , Adult , Aged , Biopsy/adverse effects , Biopsy/mortality , Biopsy/standards , Child , Child, Preschool , Female , Humans , Male , Middle Aged , Retrospective Studies , Stereotaxic Techniques/adverse effects , Stereotaxic Techniques/mortality , Young Adult
9.
Neurosurgery ; 88(2): 375-383, 2021 01 13.
Article in English | MEDLINE | ID: mdl-32985662

ABSTRACT

BACKGROUND: Occipital nerve stimulation (ONS) has been proposed to treat refractory chronic cluster headache (rCCH) but its efficacy has only been showed in small short-term series. OBJECTIVE: To evaluate ONS long-term efficacy in rCCH. METHODS: We studied 105 patients with rCCH, treated by ONS within a multicenter ONS prospective registry. Efficacy was evaluated by frequency, intensity of pain attacks, quality of life (QoL) EuroQol 5 dimensions (EQ5D), functional (Headache Impact Test-6, Migraine Disability Assessment) and emotional (Hospital Anxiety Depression Scale [HAD]) impacts, and medication consumption. RESULTS: At last follow-up (mean 43.8 mo), attack frequency was reduced >50% in 69% of the patients. Mean weekly attack frequency decreased from 22.5 at baseline to 9.9 (P < .001) after ONS. Preventive and abortive medications were significantly decreased. Functional impact, anxiety, and QoL significantly improved after ONS. In excellent responders (59% of the patients), attack frequency decreased by 80% and QoL (EQ5D visual analog scale) dramatically improved from 37.8/100 to 73.2/100. When comparing baseline and 1-yr and last follow-up outcomes, efficacy was sustained over time. In multivariable analysis, low preoperative HAD-depression score was correlated to a higher risk of ONS failure. During the follow-up, 67 patients experienced at least one complication, 29 requiring an additional surgery: infection (6%), lead migration (12%) or fracture (4.5%), hardware dysfunction (8.2%), and local pain (20%). CONCLUSION: Our results showed that long-term efficacy of ONS in CCH was maintained over time. In responders, ONS induced a major reduction of functional and emotional headache-related impacts and a dramatic improvement of QoL. These results obtained in real-life conditions support its use and dissemination in rCCH patients.


Subject(s)
Cluster Headache/therapy , Electric Stimulation Therapy/methods , Treatment Outcome , Adult , Aged , Female , Humans , Middle Aged , Peripheral Nerves/physiology , Quality of Life
10.
Muscle Nerve ; 42(3): 328-38, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20665509

ABSTRACT

Quantitative sensory testing with Semmes-Weinstein monofilaments suffers from several pitfalls. Our aims were to assess the reliability of these filaments for touch-pressure threshold detection, develop and validate a rapid and accurate procedure for measurements at the bedside, and establish normative data. After calibration of the monofilaments, an adaptive staircase algorithm was validated and used to establish normative data in healthy subjects. Calibration showed significant differences between manufacturer- and investigator-produced data. The relative humidity significantly affected the force exerted by the filaments. The adaptive procedure showed good accuracy and substantial time-saving. Touch-pressure thresholds showed significant gender differences (mean +/- 2 SD for females/males: 2.82-12.3/3.09-17.78 g/mm(2)). The influence of body site and age is small. Accurate use of Semmes-Weinstein monofilaments requires prior calibration, correction for humidity, and use of a validated procedure. In this study we provide normative data that can be used with our algorithm.


Subject(s)
Sensory Thresholds/physiology , Touch/physiology , Adult , Aged , Algorithms , Calibration , Female , Fingers/innervation , Fingers/physiology , Functional Laterality/physiology , Humans , Humidity , Lower Extremity/physiology , Male , Middle Aged , Physical Stimulation , Pressure , Reference Values , Reproducibility of Results , Young Adult
11.
12.
J Headache Pain ; 11(1): 23-31, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19936616

ABSTRACT

Chronic cluster headache (CCH) is a disabling primary headache, considering the severity and frequency of pain attacks. Deep brain stimulation (DBS) has been used to treat severe refractory CCH, but assessment of its efficacy has been limited to open studies. We performed a prospective crossover, double-blind, multicenter study assessing the efficacy and safety of unilateral hypothalamic DBS in 11 patients with severe refractory CCH. The randomized phase compared active and sham stimulation during 1-month periods, and was followed by a 1-year open phase. The severity of CCH was assessed by the weekly attacks frequency (primary outcome), pain intensity,sumatriptan injections, emotional impact (HAD) and quality of life (SF12). Tolerance was assessed by active surveillance of behavior, homeostatic and hormonal functions.During the randomized phase, no significant change in primary and secondary outcome measures was observed between active and sham stimulation. At the end of the open phase, 6/11 responded to the chronic stimulation(weekly frequency of attacks decrease [50%), including three pain-free patients. There were three serious adverse events, including subcutaneous infection, transient loss of consciousness and micturition syncopes. No significant change in hormonal functions or electrolytic balance was observed. Randomized phase findings of this study did not support the efficacy of DBS in refractory CCH, but open phase findings suggested long-term efficacy in more than 50% patients, confirming previous data, without high morbidity. Discrepancy between these findings justifies additional controlled studies (clinicaltrials.gov number NCT00662935).


Subject(s)
Cluster Headache/therapy , Deep Brain Stimulation/methods , Adult , Cluster Headache/psychology , Cross-Over Studies , Double-Blind Method , Electrodes, Implanted/adverse effects , Female , Follow-Up Studies , Functional Laterality/physiology , Humans , Hypothalamus/physiology , Male , Middle Aged , Pain Measurement/methods , Quality of Life , Time Factors , Treatment Outcome
13.
Sci Rep ; 10(1): 21427, 2020 12 08.
Article in English | MEDLINE | ID: mdl-33293642

ABSTRACT

The management of non-hemorrhagic arteriovenous malformations (AVMs) remains a subject of debate, even more since the ARUBA trial. Here, we report the obliteration rate, the risk of hemorrhage and the functional outcomes after Gamma Knife radiosurgery (GKRS) as first-line treatment for non-hemorrhagic AVMs treated before the ARUBA publication, in a reference university center with multimodal AVM treatments available. We retrospectively analyzed data from a continuous series of 172 patients harboring unruptured AVMs treated by GKRS as first-line treatment in our Lille University Hospital, France, between April 2004 and December 2013. The primary outcome was obliteration rate. Secondary outcomes were the hemorrhage rate, the modified Rankin Scale (mRS), morbidity and epilepsy control at last follow-up. The minimal follow-up period was of 3 years. Median age at presentation was 40 years (IQR 28; 51). Median follow-up was 8.8 years (IQR 6.8; 11.3). Median target volume was 1.9 cm3 (IQR 0.8-3.3 cm3), median Spetzler-Martin grade: 2 (IQR 1-2), median Pollock-Flickinger score: 1.07 (IQR 0.82-2.94), median Virginia score: 1 (IQR 1-2). Median treatment dose was 24 Gy at 50% isodose line. Twenty-three patients underwent a second GKRS after a median time of 58 months after first GKRS. The overall obliteration rate was of 76%, based primarily on cerebral angiography and/or rarely only upon MRI. Hemorrhage during the post-treatment follow-up was reported in 18 (10%) patients (annual risk of 1.1%). Transient post-GKRS morbidity was reported in 14 cases (8%) and persistent neurological deficit in 8 (4.6%) of patients. At last follow-up, 86% of patients had a mRS ≤ 1. Concerning patients with pretherapeutic epilepsy, 84.6% of them were seizure-free at last follow-up. GKRS as first-line therapeutic option for unruptured cerebral AVMs achieves high obliteration rates (76%) while maintaining a high-level patient's autonomy. All hemorrhagic events occurred during the first 4 years after the initial GKRS. In cases with epilepsy, there was 84.6% seizure free at last follow-up. Permanent morbidity was reported in only 4.6%.


Subject(s)
Epilepsy/epidemiology , Hemorrhage/epidemiology , Intracranial Arteriovenous Malformations/radiotherapy , Radiosurgery/methods , Adult , Cerebral Angiography , Epilepsy/etiology , Female , France , Hemorrhage/etiology , Humans , Intracranial Arteriovenous Malformations/diagnostic imaging , Kaplan-Meier Estimate , Male , Middle Aged , Radiosurgery/adverse effects , Retreatment/statistics & numerical data , Retrospective Studies , Treatment Outcome
14.
J Neuropathol Exp Neurol ; 68(6): 633-41, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19458546

ABSTRACT

Glioblastomas (GBMs) are highly malignant tumors characterized by microvascular proliferation and the pseudopalisading pattern of necrosis. Investigations have, therefore, focused on vascular and endothelial cell biology in GBM. Endocan, also called endothelial cell-specific molecule-1, is a proteoglycan that is secreted by endothelial cells and upregulated by proangiogenic factors. We found that endocan is not only expressed in vitro by endothelial cells but also in the T98G and U118MG human GBM cell lines. In U118MG cells, tumor necrosis factor and fibroblast growth factor 2 upregulated endocan production, whereas exposure to hypoxia or cobalt chloride, an inducer of hypoxia inducible factor 1, increased endocan release without affecting cell viability. Endocan expression in 82 brain tumors was studied by immunohistochemistry. Endocan immunoreactivity was detected in hyperplastic endothelial cells in high-grade gliomas, mostly at the tumor margins; endothelial cells were mostly endocan negative in low-grade gliomas, and it was never detected in the cerebral cortex distant from the tumors. Tumor cells in high-grade but not low-grade gliomas also expressed endocan, and it was detected in palisading cells surrounding areas of necrosis in GBM. Endothelial cell endocan immunoreactivity also correlated with shorter survival in glioma patients. Taken together, these results suggest that endocan is associated with abnormal vasculature in high-grade gliomas.


Subject(s)
Brain Neoplasms/metabolism , Gene Expression Regulation, Neoplastic/physiology , Glioblastoma/metabolism , Neoplasm Proteins/metabolism , Proteoglycans/metabolism , Adult , Aged , Brain Neoplasms/classification , Brain Neoplasms/mortality , Cell Line, Tumor , Enzyme-Linked Immunosorbent Assay/methods , Female , Follow-Up Studies , Gene Expression Regulation, Neoplastic/drug effects , Glioblastoma/classification , Glioblastoma/mortality , Humans , Hypoxia/metabolism , Hypoxia/physiopathology , Male , Middle Aged , Survival Analysis , Time Factors , Tumor Necrosis Factor-alpha/pharmacology
15.
Glia ; 57(4): 362-79, 2009 Mar.
Article in English | MEDLINE | ID: mdl-18803307

ABSTRACT

Studies in rodents have shown that astroglial erbB tyrosine kinase receptors are key regulatory elements in neuron-glia communication. Although both astrocytes and deregulation of erbB functions have been implicated in the pathogenesis of many common human brain disorders, erbB signaling in native human brain astrocytes has never been explored. Taking advantage of our ability to perform primary cultures from the cortex and the hypothalamus of human fetuses, we conducted a thorough analysis of erbB signaling in human astrocytes. We showed that human cortical astrocytes express erbB1, erbB2, and erbB3, whereas human hypothalamic astrocytes express erbB1, erbB2, and erbB4 receptors. Ligand-dependent activation of different erbB receptor heterodimeric complexes in these two populations of astrocytes translated into different morphological and proliferative responses. Although morphological plasticity was more pronounced in hypothalamic astrocytes than in cortical astrocytes, the former showed a lower mitogenic potential. Decreasing erbB4 expression via siRNA-mediated gene knockdown revealed that erbB4 constitutively restrains basal proliferative activity in hypothalamic astrocytes. We further show that treatment of human astrocytes with a protein kinase C activator results in rapid tyrosine phosphorylation of erbB receptors that involves cleavage of endogenous membrane bound erbB ligands by metalloproteinases. Together, these results indicate that erbB signaling in primary human brain astrocytes is functional, region-specific, and can be activated in a paracrine and/or autocrine manner. In addition, by revealing that some aspects of astroglial erbB signaling are different between human and rodents, our results provide a molecular framework to explore the potential involvement of astroglial erbB signaling deregulation in human brain disorders.


Subject(s)
Astrocytes/physiology , Cerebral Cortex/cytology , ErbB Receptors/metabolism , Hypothalamus/cytology , Signal Transduction/physiology , Analysis of Variance , Bromodeoxyuridine , Cell Proliferation , Cells, Cultured , ErbB Receptors/genetics , Excitatory Amino Acid Transporter 1/metabolism , Fetus , Gene Expression Regulation/drug effects , Glial Fibrillary Acidic Protein/metabolism , Humans , Immunoprecipitation/methods , Microtubule-Associated Proteins/metabolism , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Neuregulin-1/pharmacology , RNA, Small Interfering/pharmacology , Receptor, ErbB-4 , Signal Transduction/drug effects , Transforming Growth Factor alpha/pharmacology , Tyrosine/metabolism , Vimentin/metabolism
16.
Lancet Neurol ; 8(8): 709-17, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19576854

ABSTRACT

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.


Subject(s)
Athetosis/therapy , Cerebral Palsy/therapy , Chorea/therapy , Deep Brain Stimulation/methods , Dystonia/therapy , Globus Pallidus/physiology , Adult , Athetosis/complications , Basal Ganglia/pathology , Cerebral Palsy/complications , Chorea/complications , Disability Evaluation , Dystonia/complications , Female , Functional Laterality , Humans , Magnetic Resonance Imaging/methods , Male , Pilot Projects , Prospective Studies , Severity of Illness Index , Statistics, Nonparametric , Young Adult
17.
J Neurol Sci ; 278(1-2): 71-6, 2009 Mar 15.
Article in English | MEDLINE | ID: mdl-19106001

ABSTRACT

OBJECTIVES: We investigated the long-term effects and predictive indices of efficacy of tibial nerve neurotomy in a large series of patients with post-stroke hemiplegia. METHODS: Fifty-one patients were prospectively included, who showed disabling lower limb deformity (equinus, varus, clawing toes). The motor branches of the tibial nerve were selected according to the type of deformity, and partially resected at the posterior part of the calf. Patients were regularly assessed, before surgery and from the third month to the second year post surgery, for spasticity (primary outcome measure), motor control, range of active and passive movements, balance, walk, gait parameters, Rivermead Motor Assessment (RMA), subjective improvement and satisfaction. RESULTS: Neurotomy definitely reduced spasticity and improved motor control on antagonist muscles, while improving balance, walk, and the RMA. These effects were clearly perceived in daily living. A discrete decline was at times observed at 2 years. Functional improvement was greater in patients more severely impaired. Side effects, consisting in sensory disorders, were observed following neurotomy of the motor fascicles of the flexor digitorum longus. CONCLUSIONS: Tibial nerve neurotomy showed great and lasting effects, and can be proposed to improve walking and balance in stroke patients with disabling lower limb deformity.


Subject(s)
Hemiplegia/surgery , Lower Extremity/surgery , Muscle Spasticity/surgery , Stroke/complications , Tibial Nerve/surgery , Activities of Daily Living , Adult , Aged , Aged, 80 and over , Analysis of Variance , Electric Stimulation , Hemiplegia/etiology , Humans , Lower Extremity/physiopathology , Middle Aged , Motor Activity , Muscle Spasticity/etiology , Postural Balance , Range of Motion, Articular , Stroke/therapy , Treatment Outcome , Young Adult
18.
N Engl J Med ; 352(5): 459-67, 2005 Feb 03.
Article in English | MEDLINE | ID: mdl-15689584

ABSTRACT

BACKGROUND: Severe forms of dystonia respond poorly to medical treatment. Deep-brain stimulation is a reversible neurosurgical procedure that has been used for the treatment of dystonia, but assessment of its efficacy has been limited to open studies. METHODS: We performed a prospective, controlled, multicenter study assessing the efficacy and safety of bilateral pallidal stimulation in 22 patients with primary generalized dystonia. The severity of dystonia was evaluated before surgery and 3, 6, and 12 months postoperatively during neurostimulation, with the use of the movement and disability subscores of the Burke-Fahn-Marsden Dystonia Scale (range, 0 to 120 and 0 to 30, respectively, with higher scores indicating greater impairment). Movement scores were assessed by a review of videotaped sessions performed by an observer who was unaware of treatment status. At three months, patients underwent a double-blind evaluation in the presence and absence of neurostimulation. We also assessed the patients' quality of life, cognition, and mood at baseline and 12 months. RESULTS: The dystonia movement score improved from a mean (+/-SD) of 46.3+/-21.3 before surgery to 21.0+/-14.1 at 12 months (P<0.001). The disability score improved from 11.6+/-5.5 before surgery to 6.5+/-4.9 at 12 months (P<0.001). General health and physical functioning were significantly improved at month 12; there were no significant changes in measures of mood and cognition. At the three-month evaluation, dystonia movement scores were significantly better with neurostimulation than without neurostimulation (24.6+/-17.7 vs. 34.6+/-12.3, P<0.001). There were five adverse events (in three patients); all resolved without permanent sequelae. CONCLUSIONS: These findings support the efficacy and safety of the use of bilateral stimulation of the internal globus pallidus in selected patients with primary generalized dystonia.


Subject(s)
Deep Brain Stimulation , Dystonia/therapy , Globus Pallidus , Adolescent , Adult , Benzodiazepines/therapeutic use , Cholinergic Antagonists/therapeutic use , Combined Modality Therapy , Deep Brain Stimulation/adverse effects , Double-Blind Method , Dystonia/drug therapy , Electrodes, Implanted , Female , Globus Pallidus/surgery , Humans , Male , Middle Aged , Prospective Studies , Quality of Life , Treatment Outcome
19.
J Neurosurg ; 109 Suppl: 173-8, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19123905

ABSTRACT

OBJECT: Stereotactic radiosurgery is an increasingly used, and the least invasive, surgical option for patients with trigeminal neuralgia (TN). In this study, the authors performed a retrospective evaluation of the safety and efficacy of this method for idiopathic TN. METHODS: The authors reviewed data from 76 patients with idiopathic TN who underwent Gamma Knife surgery (GKS). The mean age of the patients was 64 years (range 27-83 years). All patients had typical features of TN. Thirty patients (39.5%) had previously undergone surgery. The intervention consisted of GKS on the retrogasserian cisternal portion of the fifth cranial nerve. The mean maximum GKS dose used was 85.1 Gy (range 75-90 Gy). RESULTS: Patients were followed-up from 6 to 42 months (mean 20.3 months) after GKS. Complete pain relief was achieved in 83.1% of the patients within 1 year, 70.9% within 2 years, and 62.5% within 3 years. Patients who underwent previous surgery demonstrated a lower rate of pain relief (p < 0.05). Twenty patients (26.3%) reported pain recurrence between 6 and 42 months after treatment. New or worsened persistent trigeminal dysfunction developed after GKS in 16 patients (21%); 8 of these patients described some facial numbness/not bothersome, and 8 reported some facial numbness/somewhat bothersome. None of the patients developed troublesome dysesthesia or anesthesia dolorosa. CONCLUSIONS: Gamma Knife surgery for idiopathic TN proved to be safe and effective and was associated with a particularly low rate of complications.


Subject(s)
Radiosurgery , Trigeminal Neuralgia/surgery , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Pain Measurement , Retrospective Studies , Rhizotomy , Treatment Outcome , Trigeminal Neuralgia/etiology , Trigeminal Neuralgia/pathology
20.
J Neurosurg ; 128(5): 1372-1379, 2018 05.
Article in English | MEDLINE | ID: mdl-28621622

ABSTRACT

OBJECTIVE Glossopharyngeal neuralgia (GPN) is a rare and disabling condition. Just as for trigeminal neuralgia, Gamma Knife radiosurgery (GKRS) is increasingly proposed as a therapeutic option for GPN. The purpose of this study was to assess long-term safety and efficacy of GKRS for this indication. METHODS From 2007 to 2015, 9 patients (4 male and 5 female) underwent a total of 10 GKRS procedures. All of the patients presented with GPN that was refractory to all medical treatment, and all had a long history of pain. One patient had previously undergone surgical microvascular decompression. In 5 cases, a neurovascular conflict had been identified on MRI. For the GKRS procedure, the glossopharyngeal nerve was localized on MRI and CT under stereotactic conditions. The target was located at the glossopharyngeal meatus of the jugular foramen. The dose administered to the nerve was 80 Gy in 3 procedures and 90 Gy in the others. Follow-up was planned for 3, 6, and 12 months after the procedure and annually thereafter. RESULTS Eight patients experienced an improvement in their pain. The median length of time from GKRS to symptom improvement in this group was 7 weeks (range 2-12 months). At the first follow-up, 6 patients were pain-free (pain intensity scores of I-III, based on an adaptation of the Barrow Neurological Institute scoring system for trigeminal neuralgia), including 4 patients who were also medication-free (I). One patient had partial improvement (IV) and 2 patients had no change. The mean duration of follow-up was 46 months (range 10-90 months). At the last follow-up 6 patients remained pain-free (pain scores of I-III), including 4 patients who were pain free with no medication (I). No side effect was observed. CONCLUSIONS Because of its safety and efficacy, GKRS appears to be a useful tool for treatment of GPN, including first-line treatment.


Subject(s)
Cranial Nerve Neoplasms/radiotherapy , Glossopharyngeal Nerve Diseases/radiotherapy , Radiosurgery , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Radiosurgery/adverse effects , Time Factors , Treatment Outcome
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