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Rosette-forming glioneuronal tumors (RGNT) are rare low-grade primary central nervous system (CNS) tumors. The methylation class (MC) RGNT (MC-RGNT) delineates RGNT from other neurocytic CNS tumors with similar histological features. We performed a comprehensive molecular analysis including whole-exome sequencing, RNAseq, and methylome on 9 tumors with similar histology, focusing on the immune microenvironment and cell of origin of RGNT. Three RGNT in this cohort were plotted within the MC-RGNT and characterized by FGFR1 mutation plus PIK3CA or NF1 mutations. RNAseq analysis, validated by immunohistochemistry, identified 2 transcriptomic groups with distinct immune microenvironments. The "cold" group was distinguishable by a low immune infiltration and included the 3 MC-RGNT and 1 MC-pilocytic astrocytoma; the "hot" group included other tumors with a rich immune infiltration. Gene set enrichment analysis showed that the "cold" group had upregulated NOTCH pathway and mainly oligodendrocyte precursor cell and neuronal phenotypes, while the "hot" group exhibited predominantly astrocytic and neural stem cell phenotypes. In silico deconvolution identified the cerebellar granule cell lineage as a putative cell of origin of RGNT. Our study identified distinct tumor biology and immune microenvironments as key features relevant to the pathogenesis and management of RGNT.

Anterior fossa dural arteriovenous fistulas (AF-DAVF) usually display a cortical venous drainage and are therefore at risk for rupture. Microsurgery is traditionally considered in many centers as the first-line treatment since endovascular treatment (EVT) entails a lower cure rate and significant ophthalmic risks. The anterior interhemispheric approach (AIA), originally described by Mayfrank in 1996, seems to offer the effectiveness of microsurgery while limiting the risks related to subfrontal craniotomy. The objective of this study was to analyze the surgical outcomes of patients who underwent this surgical approach for the treatment of AF-DAVF. We hereby describe our 10 years' experience of patients treated for an AF-DAVF with this technique in our institution and retrospectively analyzed our results. In addition, we describe our operative technique and its specificities. Eleven patients with AF-DAVF were included in our study. The definitive cure of the fistula was confirmed in all cases with postoperative cerebral angiography. All patients had a good neurological outcome and no major complication occurred. Brain retractors were never used during surgery, the frontal sinus was never opened neither, and anosmia was never observed after surgery. Anterior interhemispheric approach seems to be safe and effective to treat AF-DAVF with lower risks than other surgical approaches. This technique could be more widely considered when facing such midline vascular lesion.

International audience; INTRODUCTION: There is a growing interest in personality evaluation in Parkinson's disease (PD), following observations of specific temperaments in PD patients. Therefore, our objective was to evaluate personality dimensions from the Temperament and Character Inventory (TCI) in a cohort of fluctuating PD patients considered for deep brain stimulation. METHODS: Fluctuating PD patients from the PREDISTIM cohort were included. Description of TCI dimensions and comparison with a French normative cohort were performed. Pearson correlations between TCI dimensions and motor, behavioral and cognitive variables were investigated. Structural and internal consistency analysis of the TCI were further assessed. RESULTS: The 570 PD patients presented significant higher scores in Harm Avoidance, Reward Dependence, Persistence, Self-Directedness and Cooperativeness and significant lower scores in Self-Transcendence compared to the French normative cohort; only Novelty Seeking scores were not different. Harm Avoidance and Self-directedness scores were correlated with PDQ-39 total, HAMD, HAMA scores, and anxiolytic/antidepressant treatment. Novelty Seeking scores were correlated with impulsivity. Pearson correlations between TCI dimensions, principal component analysis of TCI sub-dimensions and Cronbach's alpha coefficients showed adequate psychometric proprieties. CONCLUSION: The TCI seems to be an adequate tool to evaluate personality dimensions in PD with good structural and internal consistencies. These fluctuating PD patients also have specific personality dimensions compared to normative French population. Moreover, Harm Avoidance and Self-Directedness scores are associated with anxio-depressive state or quality of life and, and Novelty Seeking scores with impulsivity.

Anterior fossa dural arteriovenous fistulas (AF-DAVF) usually display a cortical venous drainage and are therefore at risk for rupture. Microsurgery is traditionally considered in many centers as the first-line treatment since endovascular treatment (EVT) entails a lower cure rate and significant ophthalmic risks. The anterior interhemispheric approach (AIA), originally described by Mayfrank in 1996, seems to offer the effectiveness of microsurgery while limiting the risks related to subfrontal craniotomy. The objective of this study was to analyze the surgical outcomes of patients who underwent this surgical approach for the treatment of AF-DAVF. We hereby describe our 10 years' experience of patients treated for an AF-DAVF with this technique in our institution and retrospectively analyzed our results. In addition, we describe our operative technique and its specificities. Eleven patients with AF-DAVF were included in our study. The definitive cure of the fistula was confirmed in all cases with postoperative cerebral angiography. All patients had a good neurological outcome and no major complication occurred. Brain retractors were never used during surgery, the frontal sinus was never opened neither, and anosmia was never observed after surgery. Anterior interhemispheric approach seems to be safe and effective to treat AF-DAVF with lower risks than other surgical approaches. This technique could be more widely considered when facing such midline vascular lesion.

International audience; Background: For nonneoplastic neurological diseases, no recommendation exists regarding the place or appropriate timing of brain biopsy. The aim of this study was to evaluate the diagnostic yield and safety of brain biopsies from patients with neurological diseases of unknown etiology.Methods: We performed a retrospective cohort study from January 1, 2008 to December 31, 2018. We analyzed 1847 brain-biopsied patients, including 178 biopsies indicated for neurological diseases of unknown etiology. Specific histological and final diagnosis rates, positive diagnosis-associated factors, complication rate and complication-associated factors were assessed.Results: Specific histological diagnosis and final diagnosis rates were 71.3% and 83.1%, respectively, leading to therapeutic management change(s) for 75.3% of patients. Brain- biopsy-related mortality and permanent neurological morbidity occurred in 1.1% and 0.6% of the patients, respectively. The multivariable logistic-regression model retained (odds ratio [95% CI] only immunodepression (2.2 [1.1-4.7]; P=.04) as being independently associated with specific histological diagnosis, while supratentorial biopsy-targeted lesions (4.1 [1.1-15.2]; P=.04) were independently associated with a final diagnosis. Biopsies obtained from comatose patients were less contributive to the diagnosis (0.2 [0.05-0.7]; P=.01). Prebiopsy platelet count

Background Good short-term results of pallidal deep brain stimulation have been reported in myoclonus-dystonia. Efficacy and safety in the long term remain to be established. In addition, the actual impact of DBS treatment on social inclusion is unknown. The objective of this study was to assess the long-term clinical outcome, quality of life, and social adjustment of GPi-DBS in patients with e-sarcoglycan (DYT11)-positive myoclonus-dystonia. Methods Consecutive myoclonus-dystonia patients with e-sarcoglycan mutations who underwent GPi-DBS were evaluated at least 5 years postoperatively. Motor symptoms were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale including the Disability Scale, a composite score combining the rest and action parts of the Unified Myoclonus Rating Scale and modified Abnormal Involuntary Movement Scale. Standardized video-protocols were assessed by a blinded and external movement disorder specialist. Social adjustment, cognition, and mood were evaluated. Results Nine patients (5 women) with long-term GPi-DBS (8.7 ± 3.1 years) were included. There was significant improvement in the composite myoclonus score (94.1% ± 4% improvement; P = 0.008). Dystonia severity was also markedly improved (71.4% ± 28.33% improvement; P = 0.008) as well as motor disability (88.3% ± 20% improvement; P = 0.008) and abnormal involuntary movement score (71.1% ± 15.0% improvement; P = 0.008). No patients experienced postoperative speech or gait problems or any permanent adverse effects. Eight of the 9 patients had fully enhanced social adjustment and personal achievement, with little or no mood or behavioral disorders. Conclusions GPi-DBS seems to be a safe and efficacious treatment for medically refractory ɛ-sarcoglycan myoclonus-dystonia, with sustained motor benefit, good quality of life, and social adjustment in long-term follow-up. © 2018 International Parkinson and Movement Disorder Society.

Skull base meningiomas may present as clinically aggressive tumors despite being histologically benign. Here we describe a clinico-radiological entity of diffuse midline skull base meningiomas responsible for several neurological morbidities, including hearing and vision loss, intracranial hypertension, secondary hydrocephalus and tonsillar herniation with spinal cord compression. Surgery and radiotherapy were ineffective in stopping the clinical course of those tumors. After targeted sequencing of known mutated genes in meningiomas, we discovered TRAF7 mutations in two out of four tumors, stressing the importance of focusing the research efforts of the meningioma community in understanding the mechanisms underlying TRAF7 related meningioma tumorigenesis.

ResumenObjetivoDescribir la situación funcional y la autopercepción de salud de los pacientes con osteoartritis (OA) en atención primaria, comprobando su relación con el nivel de actividad física y las características sociodemográficas.DiseñoEstudio de prevalencia y asociación cruzada.EmplazamientoConsultas de medicina de familia.ParticipantesPacientes adultos diagnosticados en su historia clínica de OA de cualquier localización articular. De un total de 487, participaron 346 (71,0%).Mediciones principalesCapacidad funcional (escala WOMAC), nivel de autopercepción de salud (cuestionario EuroQoL-5D), nivel de actividad física (cuestionario IPAQ), número de articulaciones afectadas, nivel de dolor (EVA) y características sociodemográficas.ResultadosEn la escala WOMAC se obtuvo una puntuación media de 30,2 (DE: 20,8; IC95%: 28,0-32,4), correspondiendo a dolor, rigidez y capacidad funcional puntuaciones de 6,5 (DE: 4,8), 1,9 (DE: 2,0) y 21,7 (DE: 15,7), respectivamente. La puntuación presentó una tendencia lineal (p

Fundamentos: Al igual que en otros problemas crónicos, en el abor - daje del paciente con artrosis se tiende a un modelo de toma de decisiones compartidas, en el que el punto de vista del paciente debe ser considerado en la elección del tratamiento. El objetivo de este trabajo fue evaluar la sa - tisfacción con el tratamiento en pacientes diagnosticados de osteoartrosis y comprobar si existen diferencias entre diferentes opciones farmacológicas, así como determinar si existe asociación con el estado funcional y las carac - terísticas clínicas y sociodemográficas. Métodos: Se realizó un estudio observacional transversal en una muestra de 487 pacientes seleccionados mediante muestreo consecutivo. La variable principal fue el nivel de satisfacción con el tratamiento (cuestionario ARTS). El estado funcional de los pacientes fue evaluado mediante la escala WO - MAC. Otras variables fueron: características del tratamiento, adherencia te - rapéutica, eventos adversos, y variables clínicas y sociodemográficas. Resultados: En el cuestionario ARTS los pacientes, en un rango entre 28 y 87, obtuvieron una puntuación media de 65,3 (DE: 9,9). La puntuación no fue significativamente diferente en consumidores de 1, 2 o más fármacos. Entre quienes consumían un solo fármaco, no hubo diferencias entre los di - ferentes tipos de fármacos. En el estado funcional se obtuvo una puntuación media de 30,2 puntos (DE: 20,8) y se observó una débil correlación negativa con el nivel de satisfacción (r= - 0,252; p

Resumen El mesotelioma maligno es un tumor agresivo de superficies serosas cuya frecuencia esta aumentando en todo el mundo, probablemente en relacion con la exposicion extendida de la poblacion a asbesto, principal factor de riesgo con el que se ha asociado. El tratamiento actual incluye: cirugia (pleurectomia o neumonectomia extrapleural) seguida de radioterapia, aunque recientemente se ha anadido el uso de quimioterapia. El tratamiento paliativo puede contribuir a mejorar la calidad de vida y a alcanzar un buen control sintomatico durante anos tras el diagnostico. A continuacion presentamos un caso representativo de mesotelioma.

ObjectiveTo characterize how disease progression is associated with mortality in a large cohort of patients with Parkinson disease (PD) with long-term follow-up after subthalamic nucleus deep brain stimulation (STN-DBS).MethodsMotor and cognitive disabilities were assessed before and 1, 2, 5, and 10 years after STN-DBS in 143 consecutive patients with PD. We measured motor symptoms “off” and “on” levodopa and STN-DBS and recorded causes of death. We used linear mixed models to characterize symptom progression, including interactions between treatment conditions and time to determine how treatments changed efficacy. We used joint models to link symptom progression to mortality.ResultsMedian observation time was 12 years after surgery, during which akinesia, rigidity, and axial symptoms worsened, with mean increases of 8.8 (SD 6.5), 1.8 (3.1), and 5.4 (4.1) points from year 1–10 after surgery (“on” dopamine/“on” STN-DBS), respectively. Responses to dopaminergic medication and STN-DBS were attenuated with time, but remained effective for all except axial symptoms, for which both treatments and their combination were predicted to be ineffective 20 years after surgery. Cognitive status significantly declined. Forty-one patients died, with a median time to death of 9 years after surgery. The current level of axial disability was the only symptom that significantly predicted death (hazard ratio 4.30 [SE 1.50] per unit of square-root transformed axial score).ConclusionsWe quantified long-term symptom progression and attenuation of dopaminergic medication and STN-DBS treatment efficacy in patients with PD and linked symptom progression to mortality. Axial disability significantly predicts individual risk of death after surgery, which may be useful for planning therapeutic strategies in PD.

To assess efficacy and safety of hypofractionated radiation therapy (HRT) in patients over 80 years old with newly diagnosed glioblastoma (GBM). Between June 2009 and September 2015, patients in this population with a recommendation for radiation therapy from a multidisciplinary tumor board, and a Karnofsky performance status (KPS) ≥60 as assessed by a radiation oncologist, who received HRT (40 Gy/15 fractions) ± concomitant and adjuvant temozolomide (TMZ) were retrospectively analyzed. A total of 21 patients fulfilled the criteria for eligibility. Median KPS was 80 (60–90). After a median follow-up of 5.8 months (IQR 3.7–13.1 months), median overall survival (OS) was 7.5 months (95 % CI 4.5–19.1) and the 1-year and 2-year OS were 39.5 % (95 % CI 21.9–71.2 %) and 6.6 % (95 % CI 1.0− 43.3 %), respectively. Median progression-free survival (PFS) was 5.8 months (95 % CI 3.9–7.7 months), 1-year and 2-year PFS were 15.2 % (95 % CI 4.4–52.4) and 0 %, respectively. Overall, 16 (76.2 %) patients presented a recurrence. Overall seven patients (33.3 %) needed to be hospitalized during treatment. On univariate analysis, hospitalization was the only variable that correlated with less favourable outcome in terms of both OS (12.2 months versus 3.8 months, p < 0.010) and PFS (5.8 months versus 3.4 months, p = 0.002). Our study suggests that HRT is feasible with acceptable tolerance among “very elderly” patients affected by GBM. Patients 80 and older should be considered for management based on RT.

Delayed onset of non-ischemic cerebral enhancing (NICE) lesions is a rare complication of intracranial aneurysms’ endovascular therapy (EVT). The purpose of this study is to report this rare complication and its potential pathophysiology in a single-center case series and review the relevant literature. After retrospective review of all patients managed by EVT at our institution from January 1, 2012 to December 31, 2014, 2 out of 374 patients (0.5 %) with such a complication were identified. Skin patch testing was performed with all endovascular devices used in the two patients and with the European baseline series, including nickel. All previously published cases in the English literature were reviewed based on exhaustive PubMed and Embase research. Patient no. 1 developed NICE lesions 1 month after balloon-assisted coiling of a ruptured anterior communicating artery aneurysm. Patient no. 2 developed NICE lesions 12 months (the longest delay reported to date for such a complication) after the treatment of a right carotid-ophthalmic aneurysm by loose coiling and flow diversion. Patient no. 2 demonstrated nickel skin reactivity, but none of the two patients presented allergic reaction to the devices used during interventions. Based on our observations and review of the literature, we hypothesize that delayed non-ischemic cerebral enhancing lesions after EVT are more likely related to foreign body emboli rather than nickel allergy. The two presented cases demonstrate the potential for recurrence and prolonged fluctuation of NICE lesions, warranting long-term follow-up for all patients presenting this complication.

Introduction Freezing of gait (FOG) and falls are the most disabling motor symptoms in Parkinson's disease (PD) patients. The effects of subthalamic deep-brain-stimulation (STN-DBS) on FOG and falls are still a matter of controversy, and factors contributing to their outcome have yet to be defined. Methods We examined the relationship between FOG and falls after STN-DBS and preoperative clinical features, MRI voxel-based-morphometry (VBM) analysis and statistical mapping of electrode locations. Results 331 patients (age at surgery = 57.7 ± 8.4 years; disease duration = 12.5 ± 5 years) were included in the final analysis, with VBM analysis in 151 patients. After surgery, FOG was aggravated in 93 patients and falls in 75 patients. After surgery, FOG severity was related to its level before surgery without dopaminergic treatment, the dopaminergic treatment dosage and severity of motor fluctuations after surgery; and falls severity to lower postoperative cognitive performance. VBM analyses revealed that, relative to other patient groups, patients with FOG worsening had putamen grey matter density decrease, and fallers patients a left postcentral gyrus atrophy. The best effects of STN-DBS on FOG and falls were associated with the location of contacts within the STN, but no specific location related to aggravation. Conclusions FOG and falls are reduced after STN-DBS in about 1/3 of patients, with the best effects obtained for electrodes located within the STN. Clinicians should be aware that, after STN-DBS, FOG severity is related to preoperative FOG severity whatever its dopa-sensitivity; and falls to lower postoperative cognitive performance; and atrophy of cortico-subcortical brain areas.

Background Myoclonus–dystonia related to epsilon-sarcoglycan gene mutations is characterized by myoclonic jerks and mild to moderate dystonia. The role of basal ganglia dysfunction in the pathogenesis is unknown. Methods Pallidal neuronal activity was recorded in six myoclonus–dystonia and six primary generalized dystonia patients operated on for internal globus pallidus deep brain stimulation. Results In myoclonus–dystonia patients compared with primary-dystonia patients, internal pallidum neurons showed higher burst frequency, lower mean burst, and pause durations. External pallidum neurons showed higher mean pause frequency. Oscillatory activity was present in 33% and 35% of internal pallidum neurons in myoclonus–dystonia and primary-dystonia patients, respectively, predominantly in the theta frequency band (3-8 Hz). In myoclonus–dystonia patients with more severe myoclonus, internal pallidum neurons exhibited a higher bursting activity with high intraburst frequency and lower oscillatory activity frequency. Conclusions Myoclonus–dystonia appears to be related to specific changes in internal pallidum activity, leading to disruption in striato-pallido-thalamo-cortical circuits. © 2015 International Parkinson and Movement Disorder Society

As in other chronic problems, the approach of the patient with osteoarthritis tends to a shared decision-making model, in which the patient's point of view must be considered in the choice of treatment. The objetive was to evaluate treatment satisfaction in patients with osteoarthritis and to verify if there are differences between different pharmacological options, as well as to determine if there is any association with functional status and clinical and sociodemographic characteristics.A cross-sectional observational study was conducted in a sample of 487 patients selected by consecutive sampling. The main variable was the level of satisfaction with the treatment (ARTS questionnaire). The functional status of the patients was assessed using the WOMAC scale. Other variables considered were: treatment characteristics, therapeutic adherence, adverse events, and clinical and sociodemographic variables.In the ARTS questionnaire the patients, in a range between 28 and 87, obtained an average score of 65.3 (SD: 9.9). The score was not significantly different in consumers of 1, 2 or more drugs. Among those who consumed only one drug, there were no differences between the different drug types. In the functional state, an average score of 30.2 points (SD: 20.8) was obtained and a weak negative correlation was observed with the level of satisfaction (r = -0.252; p=0.001). Multiple linear regression showed a higher score on the ARTS scale (p=0.05) in patients with lower WOMAC score, older age and absence of adverse events.In patients with osteoarthritis, a moderate level of satisfaction with pharmacological treatment is observed, conditioned by their functional status, their sociodemographic characteristics and the presence of adverse events. In general, satisfaction does not depend on either the characteristics of the treatment or the number of drugs consumed.Al igual que en otros problemas crónicos, en el abordaje del paciente con artrosis se tiende a un modelo de toma de decisiones compartidas, en el que el punto de vista del paciente debe ser considerado en la elección del tratamiento. El objetivo de este trabajo fue evaluar la satisfacción con el tratamiento en pacientes diagnosticados de osteoartrosis y comprobar si existen diferencias entre diferentes opciones farmacológicas, así como determinar si existe asociación con el estado funcional y las características clínicas y sociodemográficas.Se realizó un estudio observacional transversal en una muestra de 487 pacientes seleccionados mediante muestreo consecutivo. La variable principal fue el nivel de satisfacción con el tratamiento (cuestionario ARTS). El estado funcional de los pacientes fue evaluado mediante la escala WOMAC. Otras variables fueron: características del tratamiento, adherencia terapéutica, eventos adversos, y variables clínicas y sociodemográficas.En el cuestionario ARTS los pacientes, en un rango entre 28 y 87, obtuvieron una puntuación media de 65,3 (DE: 9,9). La puntuación no fue significativamente diferente en consumidores de 1, 2 o más fármacos. Entre quienes consumían un solo fármaco, no hubo diferencias entre los diferentes tipos de fármacos. En el estado funcional se obtuvo una puntuación media de 30,2 puntos (DE: 20,8) y se observó una débil correlación negativa con el nivel de satisfacción (r= - 0,252; p=0,001). Mediante regresión lineal múltiple, se observó mayor puntuación en la escala ARTS (p=0,05) en pacientes con menor puntuación en la escala WOMAC, mayor edad y ausencia de eventos adversos.En pacientes con osteoartritis se observa un nivel moderado de satisfacción con el tratamiento farmacológico, condicionado por su situación funcional, sus características sociodemográficas y por la presencia de eventos adversos. En general, la satisfacción no depende ni de las características del tratamiento ni del número de fármacos consumidos.

Although subthalamic stimulation is a recognised treatment for motor complications in Parkinson's disease, reports on behavioural outcomes are controversial, which represents a major challenge when counselling candidates for subthalamic stimulation. We aimed to assess changes in behaviour in patients with Parkinson's disease receiving combined treatment with subthalamic stimulation and medical therapy over a 2-year follow-up period as compared with the behavioural evolution under medical therapy alone.We did a parallel, open-label study (EARLYSTIM) at 17 surgical centres in France (n=8) and Germany (n=9). We recruited patients with Parkinson's disease who were disabled by early motor complications. Participants were randomly allocated (1:1) to either medical therapy alone or bilateral subthalamic stimulation plus medical therapy. The primary outcome was mean change in quality of life from baseline to 2 years. A secondary analysis was also done to assess behavioural outcomes. We used the Ardouin Scale of Behavior in Parkinson's Disease to assess changes in behaviour between baseline and 2-year follow-up. Apathy was also measured using the Starkstein Apathy Scale, and depression was assessed with the Beck Depression Inventory. The secondary analysis was done in all patients recruited. We used a generalised estimating equations (GEE) regression model for individual items and mixed model regression for subscores of the Ardouin scale and the apathy and depression scales. This trial is registered with ClinicalTrials.gov, number NCT00354133. The primary analysis has been reported elsewhere; this report presents the secondary analysis only.Between July, 2006, and November, 2009, 251 participants were recruited, of whom 127 were allocated medical therapy alone and 124 were assigned bilateral subthalamic stimulation plus medical therapy. At 2-year follow-up, the levodopa-equivalent dose was reduced by 39% (-363·3 mg/day [SE 41·8]) in individuals allocated bilateral subthalamic stimulation plus medical therapy and was increased by 21% (245·8 mg/day [40·4]) in those assigned medical therapy alone (p0·0001). Neuropsychiatric fluctuations decreased with bilateral subthalamic stimulation plus medical therapy during 2-year follow-up (mean change -0·65 points [SE 0·15]) and did not change with medical therapy alone (-0·02 points [0·15]); the between-group difference in change from baseline was significant (p=0·0028). At 2 years, the Ardouin scale subscore for hyperdopaminergic behavioural disorders had decreased with bilateral subthalamic stimulation plus medical therapy (mean change -1·26 points [SE 0·35]) and had increased with medical therapy alone (1·12 points [0·35]); the between-group difference was significant (p0·0001). Mean change from baseline at 2 years in the Ardouin scale subscore for hypodopaminergic behavioural disorders, the Starkstein Apathy Scale score, and the Beck Depression Inventory score did not differ between treatment groups. Antidepressants were stopped in 12 patients assigned bilateral subthalamic stimulation plus medical therapy versus four patients allocated medical therapy alone. Neuroleptics were started in nine patients assigned medical therapy alone versus one patient allocated bilateral subthalamic stimulation plus medical therapy. During the 2-year follow-up, two individuals assigned bilateral subthalamic stimulation plus medical therapy and one patient allocated medical therapy alone died by suicide.In a large cohort with Parkinson's disease and early motor complications, better overall behavioural outcomes were noted with bilateral subthalamic stimulation plus medical therapy compared with medical therapy alone. The presence of hyperdopaminergic behaviours and neuropsychiatric fluctuations can be judged additional arguments in favour of subthalamic stimulation if surgery is considered for disabling motor complications.German Federal Ministry of Education and Research, French Programme Hospitalier de Recherche Clinique National, and Medtronic.

BACKGROUND Circulating proteins released by tumor cells have recently been investigated as potential single surrogate biomarkers for glioblastoma multiforme (GBM). The aim of the current hypothesis-generating study was to evaluate the diagnostic and prognostic role of preoperative insulin-like growth factor-binding protein 2 (IGFBP-2), chitinase-3-like protein 1 (YKL-40), and glial fibrillary acidic protein (GFAP) plasma levels in patients with GBM, both as single markers and as a combined profile. METHODS Plasma samples from 111 patients with GBM and a subset of 40 patients with nonglial brain tumors were obtained preoperatively. Plasma from 99 healthy controls was also analyzed. IGFBP-2, YKL-40, and GFAP levels were determined using enzyme-linked immunoadsorbent assay tests. Their association with histological and radiological variables was assessed. RESULTS Circulating levels of all 3 proteins were found to be significantly higher in patients with GBM compared with healthy controls (P < .01). Only YKL-40 and GFAP were found to demonstrate significant differences between patients with GBM and nonglial brain tumors (P = .04). GFAP was undetectable (

Spontaneous closures of dural arteriovenous fistulas (dAVFs) are rare. We present spontaneous occlusion of dAVFs in 3 cases (one type IIa dAVF, one type IIb and one type III). Patients were 3 males with a mean age of 55 years (range 45-61). For two patients, the dAVF was revealed by hemorrhage. No head trauma was recorded at the interrogatory. Mean delay for spontaneous closure was 4 months (3-5 months). Review of the literature about this rare occurrence is presented and the factors that may lead to spontaneous occlusion of dAVFs are discussed.

Resumen Objetivo Describir la situación funcional y la autopercepción de salud de los pacientes con osteoartritis (OA) en atención primaria, comprobando su relación con el nivel de actividad física y las características sociodemográficas. Diseño Estudio de prevalencia y asociación cruzada. Emplazamiento Consultas de medicina de familia. Participantes Pacientes adultos diagnosticados en su historia clínica de OA de cualquier localización articular. De un total de 487, participaron 346 (71,0%). Mediciones principales Capacidad funcional (escala WOMAC), nivel de autopercepción de salud (cuestionario EuroQoL-5D), nivel de actividad física (cuestionario IPAQ), número de articulaciones afectadas, nivel de dolor (EVA) y características sociodemográficas. Resultados En la escala WOMAC se obtuvo una puntuación media de 30,2 (DE: 20,8; IC 95%: 28,0-32,4), correspondiendo a dolor, rigidez y capacidad funcional puntuaciones de 6,5 (DE: 4,8), 1,9 (DE: 2,0) y 21,7 (DE: 15,7), respectivamente. La puntuación presentó una tendencia lineal (p

Resume Introduction La stimulation continue a haute frequence du noyau subthalamique (NST) ameliore ou fait disparaitre le tremblement de repos parkinsonien. Objectif L’objectif de ce travail etait d’evaluer le role de la stimulation du NST dans l’apparition du tremblement parkinsonien. Patients–resultats Parmi 215 patients parkinsoniens qui ont beneficie de la mise en place d’electrodes pour la stimulation des NST, 30 (14 %) avaient une forme akinetorigide, sans tremblement apres une evolution moyenne de 11 ans. Chez six d’entre eux, apres six mois de stimulation continue du NST, un tremblement « de novo » est apparu, ayant les caracteristiques cliniques du tremblement de repos de la maladie de Parkinson. Le tremblement disparaissait apres l’administration de l -dopa et des la remise en route du stimulateur. Conclusion La revelation d’un tremblement de repos apres un arret transitoire de la stimulation a haute frequence prolongee des NST suggere qu’un tremblement infraclinique caracteristique de l’affection serait en fait present chez tous les patients parkinsoniens.

The incidence of malignant gliomas is growing in the elderly population. Unfortunately, increasing age is one of the most important negative prognostic factors in gliomas and the optimal management of this population remains largely unsettled because older patients are often excluded from clinical trials. However, the classic nihilistic approach is progressively changing towards more active strategies. Particularly, prospective randomized studies have recently established the benefit of radiation therapy and the validity of an accelerated course of radiation in older patients suffering from malignant gliomas. The interest of chemotherapy, alone or concomitant with radiation therapy is still under evaluation in this population. Initial performance status, quality of life and concomitant pathologies are important factors to consider before treatment onset. In the future, it will be necessary to develop specific schedules of treatment in this population.

Background: Up-front temozolomide (TMZ) has been recently proposed as a treatment for gliomatosis cerebri (GC), but no predictive or prognostic markers have been identified so far. Because 1p19q codeletion and methylguanine methyl transferase promoter (MGMTP) methylation have been correlated with chemosensitivity of gliomas, their value was investigated in a cohort of patients with GC treated with TMZ. Methods: A cohort of 25 GC patients who were treated with TMZ was investigated for 1p19q codeletion and O6-methylguanine DNA. Results: Patients with a 1p/19q codeletion had a higher response rate (88% [8/9] vs 25% [4/16], p = 0.002), higher progression-free survival (24.5 vs 13.7 months, p = 0.017), and higher overall survival (66.8 vs 15.2 months, p = 0.011) than patients without 1p/19q codeletion. Fourteen of 19 evaluable tumors for MGMTP status were methylated. MGMTP methylation was associated with 1p/19q codeletion ( p = 0.045). Patients with unmethylated MGMTP tended to have a shorter progression-free survival and a higher rate of progressive disease. Conclusion: Response rate to temozolomide and prognosis seem tightly correlated to 1p19q loss. The impact of methylguanine methyl transferase promoter methylation status on gliomatosis cerebri is still unsettled in this population.

High-frequency stimulation of the subthalamic nucleus (STN) is an effective treatment for severe forms of Parkinson's disease (PD). To study the effects of high-frequency STN stimulation on one of the main output pathways of the basal ganglia, single-unit recordings of the neuronal activity of the substantia nigra pars reticulata (SNr) were performed before, during, and after the application of STN electrical stimulation in eight PD patients. During STN stimulation at 14 Hz, no change in either the mean firing rate or the discharge pattern of SNr neurons was observed. STN stimulation at 140 Hz decreased the mean firing rate by 64% and the mean duration of bursting mode activity of SNr neurons by 70%. The SNr residual neuronal activity during 140-Hz STN stimulation was driven by the STN stimulation. How the decrease in rate and modification of firing pattern of SNr-evoked neural activity, during high-frequency STN stimulation, contribute to the improvement of parkinsonian motor disability remains to be elucidated.

Objetivo: Determinar con qué frecuencia presentan estreñimiento los pacientes que acuden por cualquier motivo a la consulta del médico de familia y comprobar su asociación con las características sociodemográficas, la existencia de enfermedades digestivas diagnosticadas previamente y el consumo de fármacos. Diseño del estudio: Estudio de prevalencia y asociación cruzada. Emplazamiento: Atención Primaria. Participantes: Una muestra de 473 pacientes seleccionados mediante muestreo sistemático en cuatro consultas de medicina de familia. Mediciones principales: Presencia de síntomas de estreñimiento evaluado mediante la escala GSRS (Gastrointestinal Symptom Rating Scale). Otras variables: diagnóstico previo de enfermedades del aparato digestivo, consumo de medicación, frecuentación y características sociodemográficas. Resultados: El 32,0 % de los pacientes (IC 95 %: 27,5 - 36,5) declararon la presencia de síntomas de estreñimiento con intensidad moderada o fuerte: disminución de la frecuencia en el número de deposiciones, aumento en la consistencia de las heces o sensación de evacuación incompleta. Los síntomas fueron más frecuentes en mujeres (37,3 % vs. 24,0 %; p = 0,004) y en consumidores de fármacos para enfermedades del aparato digestivo (47,7 % vs. 23,8 %; p < 0,001). Se observó una tendencia lineal, estadísticamente significativa (p < 0,001), entre la presencia de estreñimiento y el número total de fármacos consumidos por los pacientes. Conclusiones: Es elevada la frecuencia de síntomas de estreñimiento en los pacientes de Atención Primaria, especialmente en el sexo femenino. Se observa una relación lineal entre la frecuencia de estos síntomas y el consumo de fármacos, por lo que el estreñimiento debe ser considerado como un potencial efecto adverso frecuente en pacientes polimedicados.

Background: The short term benefits of bilateral stimulation of the subthalamic nucleus (STN) in patients with advanced levodopa responsive Parkinson's disease (PD) are well documented, but long term benefits are still uncertain. Objectives: This study provides a 5 year follow up of PD patients treated with stimulation of the STN. Methods: Thirty seven consecutive patients with PD treated with bilateral STN stimulation were assessed prospectively 6, 24, and 60 months after neurosurgery. Parkinsonian motor disability was evaluated with and without levodopa treatment, with and without bilateral STN stimulation. Neuropsychological and mood assessments included the Mattis Dementia Rating Scale, the frontal score, and the Montgomery-Asberg Depression Rating Scale (MADRS). Results: No severe peri- or immediate postoperative side effects were observed. Six patients died and one was lost to follow up. Five years after neurosurgery: (i) activity of daily living (Unified Parkinson Disease Rating Scale (UPDRS) II) was improved by stimulation of the STN by 40% ("off" drug) and 60% ("on" drug); (ii) parkinsonian motor disability (UPDRS III) was improved by 54% ("off" drug) and 73% ("on" drug); (iii) the severity of levodopa related motor complications was decreased by 67% and the levodopa daily doses were reduced by 58%. The MADRS was unchanged, but cognitive performance declined significantly. Persisting adverse effects included eyelid opening apraxia, weight gain, addiction to levodopa treatment, hypomania and disinhibition, depression, dysarthria, dyskinesias, and apathy. Conclusions: Despite moderate motor and cognitive decline, probably due to disease progression, the marked improvement in motor function observed postoperatively was sustained 5 years after neurosurgery.

In this prospective double blind randomised "N of 1" study, a patient with a severe form of Tourette's syndrome was treated with bilateral high frequency stimulation of the centromedian-parafascicular complex (Ce-Pf) of the thalamus, the internal part of the globus pallidus (GPi), or both. Stimulation of either target improved tic severity by 70%, markedly ameliorated coprolalia, and eliminated self injuries. Severe forms of Tourette's syndrome may benefit from stimulation of neuronal circuits within the basal ganglia, thus confirming the role of the dysfunction of limbic striato-pallido-thalamo-cortical systems in this disorder.

International audience; BackgroundSubthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for the motor and non-motor signs of Parkinson’s disease (PD), however, psychological disorders and social maladjustment have been reported in about one third of patients after STN-DBS. We propose here a perioperative psychoeducation programme to limit such social and familial disruption.MethodsNineteen PD patients and carers were included in a randomised single blind study. Social adjustment scale (SAS) scores from patients and carers that received the psychoeducation programme (n = 9) were compared, both 1 and 2 years after surgery, with patients and carers with usual care (n = 10). Depression, anxiety, cognitive status, apathy, coping, parkinsonian disability, quality-of-life, carers’ anxiety and burden were also analysed.ResultsSeventeen patients completed the study, 2 were excluded from the final analysis because of adverse events. At 1 year, 2/7 patients with psychoeducation and 8/10 with usual care had an aggravation in at least one domain of the SAS (p = .058). At 2 years, only 1 patient with psychoeducation suffered persistent aggravated social adjustment as compared to 8 patients with usual care (p = .015). At 1 year, anxiety, depression and instrumental coping ratings improved more in the psychoeducation than in the usual care group (p = .038, p = .050 and p = .050, respectively). No significant differences were found between groups for quality of life, cognitive status, apathy or motor disability.ConclusionsOur results suggest that a perioperative psychoeducation programme prevents social maladjustment in PD patients following STN-DBS and improves anxiety and depression compared to usual care. These preliminary data need to be confirmed in larger studies.

International audience; Patients with surgery- and radiation-refractory meningiomas have a poor outcome. Due to our lack of knowledge concerning multi-recurrent meningioma natural history, their clinical course is poorly defined. This retrospective study aims at defining patterns of relapse in order to help in the definition of response criteria in future clinical trials. We performed a retrospective review of surgery- and radiotherapy-refractory meningioma cases with interpretable radiological follow-up treated in our department. Tumor volumes were measured on 3D T1 Gadolinium volumetric sequences using a semi-automated algorithm for tumor segmentation. Twenty nine patients with multi-treated meningioma (11 WHO Grade II, 5 de novo WHO Grade III and 13 transformed WHO Grade III), were evaluated. Median PFS was 16 months for patients with Grade II meningiomas. In patients with Grade III meningiomas, the de novo subgroup had a median PFS of 4 months compared with 7 months in patients with malignant transformation. Volumetric analysis of tumor growth concerned 95 tumor nodules in 50 relapses. The mean growth rate of tumor nodules was 10.4 cm3/year (95 % CI 7.3–14.8 cm3/year). Three patterns of tumor growth were described: “classical” for 9 (31 %) patients, “local multi-nodular” for 6 (21 %) patients and “multi-nodular metastatic” for the last 14 (48 %) patients. Considering all tumor nodules, median time to tumor progression (TTP) was 3.7 months. Progressing tumors represent the most frequent histological subgroup of surgery and radiation-refractory meningiomas while tumors with multi-nodular metastatic dissemination are the prominent radiological pattern of progression.

OBJECTIVE To further determine the causes of variable outcome from deep brain stimulation of the subthalamic nucleus (DBS-STN) in patients with Parkinson disease (PD). METHODS Data were obtained from our cohort of 309 patients with PD who underwent DBS-STN between 1996 and 2009. We examined the relationship between the 1-year motor, cognitive, and psychiatric outcomes and (1) preoperative PD clinical features, (2) MRI measures, (3) surgical procedure, and (4) locations of therapeutic contacts. RESULTS Pre- and postoperative results were obtained in 262 patients with PD. The best motor outcome was obtained when stimulating contacts were located within the STN as compared with the zona incerta (64% vs 49% improvement). Eighteen percent of the patients presented a postoperative cognitive decline, which was found to be principally related to the surgical procedure. Other factors predictive of poor cognitive outcome were perioperative confusion and psychosis. Nineteen patients showed a stimulation-induced hypomania, which was related to both the form of the disease (younger age, shorter disease duration, higher levodopa responsiveness) and the ventral contact location. Postoperative depression was more frequent in patients already showing preoperative depressive and/or residual axial motor symptoms. CONCLUSION In this homogeneous cohort of patients with PD, we showed that (1) the STN is the best target to improve motor symptoms, (2) postoperative cognitive deficit is mainly related to the surgery itself, and (3) stimulation-induced hypomania is related to a combination of both the disease characteristics and a more ventral STN location.

Myoclonus-dystonia related to epsilon-sarcoglycan gene mutations is characterized by myoclonic jerks and mild to moderate dystonia. The role of basal ganglia dysfunction in the pathogenesis is unknown.Pallidal neuronal activity was recorded in six myoclonus-dystonia and six primary generalized dystonia patients operated on for internal globus pallidus deep brain stimulation.In myoclonus-dystonia patients compared with primary-dystonia patients, internal pallidum neurons showed higher burst frequency, lower mean burst, and pause durations. External pallidum neurons showed higher mean pause frequency. Oscillatory activity was present in 33% and 35% of internal pallidum neurons in myoclonus-dystonia and primary-dystonia patients, respectively, predominantly in the theta frequency band (3-8 Hz). In myoclonus-dystonia patients with more severe myoclonus, internal pallidum neurons exhibited a higher bursting activity with high intraburst frequency and lower oscillatory activity frequency.Myoclonus-dystonia appears to be related to specific changes in internal pallidum activity, leading to disruption in striato-pallido-thalamo-cortical circuits. © 2015 International Parkinson and Movement Disorder Society.

Circulating proteins released by tumor cells have recently been investigated as potential single surrogate biomarkers for glioblastoma multiforme (GBM). The aim of the current hypothesis-generating study was to evaluate the diagnostic and prognostic role of preoperative insulin-like growth factor-binding protein 2 (IGFBP-2), chitinase-3-like protein 1 (YKL-40), and glial fibrillary acidic protein (GFAP) plasma levels in patients with GBM, both as single markers and as a combined profile.Plasma samples from 111 patients with GBM and a subset of 40 patients with nonglial brain tumors were obtained preoperatively. Plasma from 99 healthy controls was also analyzed. IGFBP-2, YKL-40, and GFAP levels were determined using enzyme-linked immunoadsorbent assay tests. Their association with histological and radiological variables was assessed.Circulating levels of all 3 proteins were found to be significantly higher in patients with GBM compared with healthy controls (P.01). Only YKL-40 and GFAP were found to demonstrate significant differences between patients with GBM and nonglial brain tumors (P = .04). GFAP was undetectable (0.02 ng/mL) in all patients without GBM. A receiver operating characteristic analysis accounting for a 2-step diagnostic procedure including the 3 biomarkers afforded an area under the curve of 0.77 for differentiating patients with GBM from those with nonglial brain tumors. There was a significant correlation between tumor volume and plasma IGFBP-2 level (Spearman Rho correlation coefficient, 0.22; P = .025) and GFAP (Spearman Rho correlation coefficient, 0.36; P.001) among patients with GBM. Preoperative plasma IGFBP-2 levels were found to be independently associated with worse overall survival among patients with GBM (hazard ratio, 1.3; P = .05).A combined profile of preoperative IGFBP-2, GFAP, and YKL-40 plasma levels could serve as an additional diagnostic tool for patients with inoperable brain lesions suggestive of GBM. In addition, IGFBP-2 levels appear to constitute an independent prognostic factor in patients with GBM.

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International audience; The aim of the present study was to evaluate the impact of first-line radiotherapy on low-grade gliomas (LGGs) growth kinetics. The mean tumor diameter (MTD) of 39 LGGs was retrospectively measured on serial magnetic resonance images before (n = 16) and after radiotherapy onset (n = 39). After radiotherapy, a decrease of the MTD was observed in 37 patients. Median duration of the MTD decrease was 1.9 years (range 0-8.1 years). According to RANO criteria, the rates of partial and minor responses were 15 and 28 % at the first evaluation after radiotherapy and 36 and 34 % at the time of maximal MTD decrease. The presence of a 1p19q codeletion and the absence of p53 expression were associated with longer durations of MTD decrease (5.3 vs 1 years, p = 0.02 and 2.4 vs 1.8 years, p = 0.05, respectively) while no association was observed between IDH1-R132H expression and duration of MTD decrease. In most patients, MTD decrease after radiotherapy occurred in two phases: an initial phase of rapid MTD decrease followed by a second phase of slower MTD decrease. Patients with a high rate of MTD decrease during the initial phase (>7 mm/year) had both a shorter duration of response (1.9 vs 5.3 years, p = 0.003) and a shorter overall survival (5.5 vs 11.6 years, p = 0.0004). LGGs commonly display a prolonged and ongoing volume decrease after radiotherapy. However, patients who respond rapidly should be carefully monitored because they are at a higher risk of rapid progression.

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Delayed onset of non-ischemic cerebral enhancing lesions is a rare complication of intracranial aneurysms’ endovascular therapy (EVT). This complication has been attributed either to foreign body emboli and subsequent granulomatous reaction or cerebral hypersensitivity and nickel allergy. After retrospective review of all patients managed by EVT at our Institution from January 1st 2012 to December 31st 2014, 2 out of 374 patients (0.5%) with such a complication were identified. Patient # 1 developed non-ischemic cerebral enhancing (NICE) lesions 1 month after balloon assisted coiling of a ruptured anterior communicating artery aneurysm. Patient # 2 developed NICE lesions 12 months (the longest delay reported to date for such complication) after the treatment of a right carotidophthalmic aneurysm by loose coiling and flow diversion. Skin patch testing was performed with all endovascular devices used in the 2 patients and with the European baseline series, including nickel. Patient # 2 demonstrated nickel skin reactivity but none of the 2 patients presented allergic reaction to the devices used during interventions. Based on our observations and review of the literature, we hypothesize that delayed non-ischemic cerebral enhancing lesions after EVT are more likely related to foreign body emboli rather than nickel allergy. Disclosures E. Shotar: None. B. Law-Ye: None. F. Di Maria: None. F. Baronnet-Chauvet: None. S. Zeidan: None. D. Psimaras: None. F. Bielle: None. C. Pecquet: None. S. Navarro: None. C. Rosso: None. F. Cohen: None. J. Chiras: None. N. Sourour: 2; C; Covidien. F. Clarencon: 2; C; Covidien, Codman.

Contexte/objectif La survenue retardee de lesions cerebrales non ischemiques prenant le contraste (non-ischemic cerebral enhancing [NICE]) est une complication rare apres embolisation d’anevrysmes intracrâniens. Cette complication a ete attribuee soit a une reaction granulomateuse a corps etrangers ou a une allergie au nickel. L’objectif de notre etude est d’evaluer la frequence de cette complication et de rechercher les causes de cette entite rare. Materiels et methodes Analyse retrospective des patients traites par voie endovasculaire pour des anevrysmes intracrâniens entre le 1er janvier 2012 et le 31 decembre 2014 dans notre institution. Les complications de type lesions NICE (confirmees en IRM) ont ete systematiquement relevees. Les signes cliniques et aspects en imagerie ont systematiquement ete evalues. Des tests epicutanes ont ete realises avec tous les outils endovasculaires utilises chez les patients atteints ainsi qu’avec la batterie standard europeenne (comprenant le nickel). Une biopsie neuro-meningee a ete realisee a 21 mois de l’embolisation chez un des deux patients identifies. Resultats Deux patients sur 374 (0,5 %) ont presente des lesions NICE. Le premier patient a developpe des lesions cerebrales prenant le contraste 1 mois apres coiling d’un anevrysme rompu de l’artere communicante anterieure. Le second patient a developpe des lesions 12 mois (le plus long delai rapporte a ce jour) apres traitement d’un anevrysme carotido-ophtalmique droit par coiling et stent flow-diverter. Le test epicutane au nickel etait positif chez le second patient. Tous les tests avec les outils endovasculaires etaient negatifs. L’analyse anatomopathologique de la piece de biopsie realisee chez le second patient a trouve une infiltration inflammatoire lymphocytaire non specifique, une reaction astrocytaire et une minime vascularite eosinophile leucocytoclasique, sans corps etranger ou cellule geante. Conclusion Sur la base des 2 cas rapportes et de la revue de la litterature, les lesions NICE sont plus vraisemblablement en rapport avec une reaction a corps etranger qu’une allergie au nickel.

Embolization of extra-axial tumors has shown its effectiveness in reducing perisurgical blood loss. However, the complication rate of this procedure is poorly reported. We aimed to evaluate the rate of procedure-related complications and their risk factors. From 1998 to 2011, 193 consecutive patients (141 females, 52 males; mean age = 52.9 years) were referred to our institution for presurgical embolization of an extra-axial tumor (meningiomas: n = 178; solitary fibrous tumors: n = 3; other: n = 12). Of 193 patients, 137 (71 %) underwent 141 embolizations (by microparticles: n = 133; by glue: n = 8). The remaining 56 patients (29 %) were not embolized due to unstable catheterization or dangerous anastomosis. Occurrence of neurological deficit was systematically assessed during and after embolization. The risk factors of procedure-related neurological complications were evaluated. Neither intratumoral hemorrhage nor procedure-related death was reported. Two of the 137 patients (1.5 %) had ischemic events with permanent neurological deficit after microparticles embolization. One patient had cortical blindness and one had hemiparesis. Both complications involved the vertebrobasilar system. The first patient had direct intratumoral anastomosis between the middle and the posterior meningeal arteries (PMA); the second one had reflux in the vertebral artery during particles injection in the PMA. Occurrence of ischemic complication was not related to the size of the microparticles. Though embolization of meningeal tumors is considered as a safe technique, serious neurological complications may occur. Opening of dangerous anastomosis or uncontrolled reflux caused two neurological complications (1.5 %). The size of the microparticles was not associated with the occurrence of neurological event.

The role of prophylactic intrathecal chemotherapy in the treatment of primary central nervous system lymphoma remains controversial. We report a retrospective single center study of a cohort of 69 patients with primary central nervous system lymphoma who had been treated with a regimen that combined high intravenous doses of Methotrexate, CCNU, procarbazine and methylprednisolone. Before 2000, patients systematically received intrathecal prophylaxis including Methotrexate, cytarabine, and hydrocortisone delivered either by intraventricular or lumbar injection along with the systemic chemotherapy (group A, n = 39). After this date, the procedure was changed and intrathecal chemotherapy was withdrawn from the protocol (group B, n = 30). The median age and Karnofsky index were comparable in both groups. At the time of analysis, we found no significant difference between patients with and without intrathecal prophylaxis in terms of objective response rate, patterns of relapse, progression-free survival or overall survival. In our study, intrathecal prophylaxis withdrawal from a high dose intravenous Methotrexate-based chemotherapy regimen did not influence disease control and outcome of primary central nervous system lymphoma. Further studies prospectively investigating the role of intrathecal chemoprophylaxis are warranted for this disease.

International audience; OBJECTIVE: To assess the efficacy of bilateral deep brain stimulation of the internal pallidum in patients with myoclonus-dystonia due to genetically proved ε-sarcoglycan (SGCE-M-D) deficiency. DESIGN: Patients with documented SGCE-M-D undergoing bilateral deep brain stimulation of the internal pallidum were recruited. Standardized assessments of M-D were videorecorded before surgery and 6 to 9 months and 15 to 18 months after surgery, using the movement and disability subscales of the Burke-Fahn-Marsden Dystonia Rating Scale and the Unified Myoclonus Rating Scale. The analysis was based on blinded evaluation of the recordings. SETTING: Movement disorder unit in a university hospital in Paris. PATIENTS: Five consecutive patients with documented SGCE-M-D. MAIN OUTCOME MEASURES: Myoclonus and dystonia scores at follow-up. RESULTS: The median myoclonus score decreased from 76 before surgery (range, 38-116) to 10 at 6 to 9 months after surgery (range, 6-31). The median dystonia score decreased from 30.0 before surgery (range, 18.5-53.0) to 4.5 after surgery (range, 3.5-16.0). Disability was also improved and symptoms remained stable between the postoperative evaluations. No adverse effects occurred. CONCLUSIONS: Bilateral deep brain stimulation of the internal pallidum is safe and highly effective in this homogeneous population of patients with SGCE-M-D. This therapeutic option should therefore be considered for patients with severe, drug-resistant forms of the disorder.

The prognosis of patients with primary CNS lymphoma (PCNSL) who fail high-dose methotrexate (HD-MTX)–based chemotherapy remains poor, particularly in older individuals, and improvements in salvage chemotherapy are needed. The few cytotoxic agents available for this condition demonstrate limited efficacy.1 Lenalidomide is an immunomodulatory agent, derived from thalidomide, with antiproliferative activities that might act by modifying the tumor microenvironment and activating cytotoxic T and natural killer cells.2 Its efficacy has been established in multiple myeloma and more recently as a single agent or in combination with rituximab in several types of non-Hodgkin lymphomas. In refractory or relapsed systemic diffuse large B-cell (DLBC) lymphomas, lenalidomide exhibited a 28%–35% response rate with a good safety profile.3,4 Interestingly, pomalidomide, a lenalidomide analog, showed activity against CNS lymphoma in murine models and is currently investigated in a phase I study (NCT 01722305). Although little is known about the capacity of lenalidomide to cross the blood–brain barrier,5 this drug appears to be potentially active in PCNSL. The objective of this retrospective case series was to determine the response rate to a standard dose of lenalidomide. Acknowledgment: The authors thank the LOC French National Network (INCa) for its support.

Background: α-Internexin (INA) is a proneural gene encoding a neurofilament interacting protein that is upregulated in some gliomas, particularly oligodendrogliomas.Methods: INA expression was evaluated by immunohistochemistry in a series of 122 gliomas, and correlated to the 1p19q codeletion, a favorable prognostic marker of oligodendroglial tumors.Results: INA expression was strong (>10% positive cells) in 22 cases (22 oligodendroglial tumors and 0 astrocytic tumors), weak (p < 0.001). In oligodendroglial tumors, INA expression specificity for 1p19q codeletion was 86%, sensitivity 96%, positive predictive value 76%, and negative predictive value was 98%. The prognostic impact of INA expression could be evaluated in grade III oligodendroglial tumors. Similar to 1p19q deletion, positive INA expression was correlated with better progression-free survival (52.6 vs 8.7 months [p = 0.001]) and overall survival (121.1 vs 31.4 months [p = 0.0001]).Conclusion: α-Internexin (INA) expression appears to be a simple, reliable prognostic marker and a surrogate marker of 1p19q codeletion.

Lumbosacral radiculopathy is a rare complication of radiotherapy and may be challenging to differentiate from diagnosis of a tumor recurrence. We reviewed the records of three patients with a past history of cancer and radiotherapy who were referred for suspicion of carcinomatous meningitis on lumbar MRI, but whose final diagnosis was radiation-induced lumbosacral radiculopathy. The three patients developed a progressive lumbosacral radiculopathy at 20, 13, and 47 years after lumbar radiotherapy delivered for renal cancer, Hodgkin’s disease, and a seminoma, respectively. MRI showed a diffuse, nodular enhancement of the cauda equina nerve roots on T1 sequences, suggestive of leptomeningeal metastasis. A slowly progressive clinical course over several years and negative cerebrospinal fluid cytologic analysis ruled out the diagnosis of carcinomatous meningitis. Because of the radiologic findings, a biopsy was performed in two patients. In the first, a biopsy limited to the arachnoid excluded a malignant infiltration. In the second, a biopsy of the enhancing lesions demonstrated spinal root cavernomas. These observations, together with three recent case reports in the literature, delineate a syndrome of “radiation-induced lumbosacral radiculopathy with multiple spinal root cavernomas” that mimics carcinomatous meningitis on MRI. Its diagnosis is important in order to avoid inappropriate treatment and useless or dangerous spinal root biopsies.

Background Tourette syndrome (TS) is thought to result from dysfunction of the associative-limbic territories of the basal ganglia, and patients with severe symptoms of TS respond poorly to medication. High-frequency stimulation has recently been applied to patients with TS in open studies using the centromedian-parafascicular complex (CM-Pf) of the thalamus, the internal globus pallidus (GPi), or the anterior limb of the internal capsule as the principal target. Objective To report the effect of high-frequency stimulation of the CM-Pf and/or the GPi, 2 associative-limbic relays of the basal ganglia, in patients with TS. Design Controlled, double-blind, randomized crossover study. Setting Medical research. Patients Three patients with severe and medically refractory TS. Intervention Bilateral placement of stimulating electrodes in the CM-Pf (associative-limbic part of the thalamus) and the GPi (ventromedial part). Main Outcome Measures Effects of thalamic, pallidal, simultaneous thalamic and pallidal, and sham stimulation on neurologic, neuropsychological, and psychiatric symptoms. Results A dramatic improvement on the Yale Global Tic Severity Scale was obtained with bilateral stimulation of the GPi (reduction in tic severity of 65%, 96%, and 74% in patients 1, 2, and 3, respectively). Bilateral stimulation of the CM-Pf produced a 64%, 30%, and 40% reduction in tic severity, respectively. The association of thalamic and pallidal stimulation showed no further reduction in tic severity (60%, 43%, and 76%), whereas motor symptoms recurred during the sham condition. No neuropsychological, psychiatric, or other long-term adverse effect was observed. Conclusions High-frequency stimulation of the associative-limbic relay within the basal ganglia circuitry may be an effective treatment of patients with TS, thus heightening the hypothesis of a dysfunction in these structures in the pathophysiologic mechanism of the disorder. Trial Registration clinicaltrials.gov Identifier:NCT00139308

International audience; BACKGROUND: We have previously reported the efficacy and safety of bilateral pallidal stimulation for primary generalised dystonia in a prospective, controlled, multicentre study with 1 year of follow-up. Although long-term results have been reported by other groups, no controlled assessment of motor and non-motor results is available. In this prospective multicentre 3 year follow-up study, involving the same patients as those enrolled in the 1 year follow-up study, we assessed the effect of bilateral pallidal stimulation on motor impairment, disability, quality of life, cognitive performance, and mood. METHODS: We studied 22 patients with primary generalised dystonia after 3 years of bilateral pallidal stimulation. We compared outcome at 3 years with their status preoperatively and after 1 year of treatment. Standardised video recordings were scored by an independent expert. Data were analysed on an intention-to-treat basis. FINDINGS: Motor improvement observed at 1 year (51%) was maintained at 3 years (58%). The improvement in quality of life (SF-36 questionnaire) was similar to that observed at 1 year. Relative to baseline and to the 1 year assessment, cognition and mood were unchanged 3 years after surgery, but slight improvements were noted in concept formation, reasoning, and executive functions. Pallidal stimulation was stopped bilaterally in three patients because of lack of improvement, technical dysfunction, and infection, and unilaterally in two patients because of electrode breakage and stimulation-induced contracture. No permanent adverse effects were observed. INTERPRETATION: Bilateral pallidal stimulation provides sustained motor benefit after 3 years. Mild long-term improvements in quality of life and attention were also observed.

Stimulation of the subthalamic nucleus is an effective treatment for advanced Parkinson disease (PD) and is currently performed after a mean disease duration of 14 years, when severe motor complications have resulted in marked loss of quality of life. We examined whether surgery at an early stage would maintain quality of life as well as improve motor function.Twenty patients with PD of short duration (time elapsed since first symptom +/- SD: 6.8 +/- 1.0 years) with mild to moderate motor signs (Unified Parkinson's Disease Rating Scale III "off" medication: 29 +/- 12) who responded well to levodopa treatment were included in pairs, matched for age, duration and severity of disease, and impairment in socioprofessional functioning. Patients were prospectively randomized to undergo bilateral subthalamic nucleus stimulation (n = 10) or receive optimized medical treatment (n = 10). Parkinsonian motor scores, quality of life, cognition, and psychiatric morbidity were assessed at inclusion and at 6, 12, and 18 months after randomization.Quality of life was improved by 24% in surgical and 0% in nonsurgical patients (p0.05). After 18 months, the severity of parkinsonian motor signs "off" medication, levodopa-induced motor complications, and daily levodopa dose were reduced by 69%, 83%, and 57% in operated patients and increased by 29%, 15%, and 12% in the group with medical treatment only (p0.001). Adverse events were mild or transient, and overall psychiatric morbidity and anxiety improved in the surgical group.Subthalamic nucleus stimulation should be considered a therapeutic option early in the course of Parkinson disease.

Background: High-frequency stimulation of the subthalamic nucleus (STN) is an effective treatment for advanced Parkinson disease (PD). The clinical and preoperative predictive factors of the best postoperative outcome have been identified. Radiologic predictive factors were investigated. Methods: Forty patients with PD underwent surgery for bilateral STN stimulation. MRI was performed in stereotactic conditions before surgery. Brain parenchyma, caudate nucleus, putamen, pallidum, and red nucleus volumes and the surface of the mesencephalon were measured and normalized as percentages of the intracranial volume. Clinical evaluation was performed 1 month before and 6 months after surgery. Results: The normalized brain parenchyma volume was lower in patients who were older and had a longer disease duration or a lower frontal score and was not predictive of the postoperative outcome. The residual scores for activities of daily living and parkinsonian motor disability were higher in patients with a smaller normalized mesencephalon. The normalized caudate nucleus volume was predictive of the pre- and postoperative levodopa-equivalent dosage. Conclusions: Brain atrophy is not an exclusion criterion for neurosurgery, indicating that patients’ neurologic, psychiatric, and neuropsychological characteristics are the best predictive factors for neurosurgery. The fact that a smaller normalized mesencephalon surface was associated with a lower beneficial effect of the subthalamic nucleus stimulation on the parkinsonian motor disability suggests that the normalized mesencephalon surface is a predictive factor of the postoperative outcome.