[Frameless trigeminal neuralgia radiosurgery with a dedicated linear accelerator: From equipment commissioning to initial clinical results]. / Radiochirurgie des névralgies trigéminales avec accélérateur linéaire dédié sans cadre invasif : de la mise en service de l'appareil aux premiers résultats cliniques.

PURPOSE: Radiosurgery for the treatment of trigeminal neuralgia delivers a very high dose in a single fraction, over a few millimeters, at a single isocenter placed along the nerve. We present here the different steps that have been performed to validate small beams by conical collimators, and report the clinical results of the first patients treated on Novalis Tx®, frameless. MATERIAL AND METHODS: First, the geometric accuracy of 4 and 6mm conical collimators was evaluated using Winston-Lutz tests; then dosimetric data acquisition was performed using high spatial resolution detectors (PTW 60019 microdiamond and a PTW 60017 E-diode). The corrective factors of the TRS 483 report were applied to calculate the collimator aperture factors. These dosimetric data were then compared with the data implemented in the iPlan® treatment planning system. Then end-to-end tests were performed to control the entire treatment process using an anthropomorphic phantom "STEEV". Between 2020 and 2022, 18 patients were treated for refractory trigeminal neuralgia on Novalis Tx®, frameless, with Exactrac® repositioning. A total of 17 patients were evaluated (one was lost to follow-up) using the BNI score for pain assessment and MRI with a median follow-up of 12 months. RESULTS: The quality criteria of geometric and dosimetric accuracy were met for the 6-mm cone but not for the 4-mm cone. All patients were treated with a 6-mm cone with a dose of 90Gy prescribed at the isocenter at the root entry zone. Initial pain control was obtained in 70.5% of our patients, and 53% maintained pain control with a median follow-up of 12 months. All recurrences occurred within 3 to 6 months after radiosurgery. No brainstem toxicity was observed. Six patients had non-disabling facial hypoesthesia, half of whom already had pretreatment hypoesthesia. CONCLUSION: The treatment of trigeminal neuralgia on a dedicated linear accelerator is a highly technical treatment whose accuracy and safety are paramount. The physical measurements allowed the commissioning of the technique with a 6mm cone. Our first clinical results are in accordance with the literature.

Neural correlates of consciousness and related disorders: From phenotypic descriptors of behavioral and relative consciousness to cortico-subcortical circuitry.

We report a review of medical aspects of the consciousness. The behavioral dimension, phenotypic descriptors, relative consciousness and neural correlates of consciousness and related disorders were addressed successively in a holistic and chronological approach. Consciousness is relative, specific to each individual across time and space. Historically defined as the perception of the self and the environment, it cannot be separated from behaviors, entailing an idea of conscious behavior with metapractic and metagnostic aspects. Observation of spontaneous and evoked overt behavior distinguishes three main types of disorder of consciousness (DoC): coma, vegetative state or unresponsive wakefulness, and minimally conscious or relationally impoverished state. Modern functional exploration techniques, such as imaging, increase the understanding of DoCs and consciousness. Whether consciousness is a superior function and/or an instrumental function is discussed. Neural correlates can be subdivided into two wakefulness pathways (superior thalamic cholinergic and inferior extra-thalamic), and cortico-subcortical circuitry. The deep brain structures are those described in the well-known sensorimotor, associative and limbic loops, as illustrated in the mesolimbic model of DoC. The cortices can be segregated into several overlapping networks: (1) a global workspace including thalamo-cortical loops; (2) the default mode network (DMN) and related intrinsic connectivity networks (i.e., central executive, medial DMN and salience networks); (3) a 3-fold network comprising the fronto-parietal control system and its dorsal and ventral attentional sub-networks, the fronto-parietal executive control network, and the cingulo-opercular salience network; (4) the internal and external cortices, respectively medial, turned toward the self, and lateral, turned toward the environment. The network dynamics is the reflection of consciousness, notably anticorrelations such as the decrease in activity of the posterior cingulate-precuneus regions during attentional tasks. Thanks to recent advances in DoC pathophysiology, further significative therapeutic progress is expected, taking into account the societal context. This depends notably on the dissemination of medical knowledge and its transfer to a wider public.

Misleading clinical presentation of carcinoid syndrome.

Rare cases of carcinoid syndromes can develop from either gastrointestinal neuroendocrine tumors (NETs) without liver metastasis or large retroperitoneal involvement. We report a case of a patient with isolated flushing highly suggestive of carcinoid syndrome caused by an ileal NET with adjacent lymph node metastases but with no liver metastases. The final diagnose was delayed for this patient due to a combination of misleading clinical presentation and negative usual screening tests (urinary 5-HIAA and serum chromogranine A). Given its high sensitivity and specificity, 68Ga-DOTATATE PET/CT confirmed the diagnosis of neuroendocrine tumor. Therefore, this case reminds clinicians that carcinoid syndrome may manifest as flushing only and highlights that imaging is a major aspect of the evaluation and diagnosis of patients with suspected gastrointestinal NETs.

Functional and dysfunctional impulsivities changes after subthalamic nucleus-deep brain stimulation in Parkinson disease.

OBJECTIVES: We investigated changes of impulsivity after deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD) patients, distinguishing functional from dysfunctional impulsivity and their contributing factors. METHODS: Data of 33 PD patients treated by STN-DBS were studied before and 6 months after surgery: motor impairment, medication (dose and dopaminergic agonists), cognition, mood and occurrence of impulse control disorders. Impulsivity was assessed by the Dickman Impulsivity Inventory, which distinguishes functional impulsivity (FI), reflecting the potential for reasoning and rapid action when the situation requires it, and dysfunctional impulsivity (DI), reflecting the lack of prior reasoning, even when the situation demands it. The location of DBS leads was studied on postoperative MRI using a deformable histological atlas and by compartmentalization of the STN. RESULTS: After STN-DBS, DI was significantly increased (mean pre- and postoperative DI scores 1.9±1.6 and 3.5±2.4, P<0.001) although FI was not modified (mean pre- and postoperative FI scores 6.2±2.7 and 5.8±2.6). Factors associated with a DI score's increase≥2 (multivariable logistic regression model) were: low preoperative Frontal Assessment Battery score and location of the left active contact in the ventral part of the STN. CONCLUSION: Our study suggests that STN-DBS may have a different impact on both dimensions of impulsivity, worsening pathological impulsivity without altering physiological impulsivity. The increase in dysfunctional impulsivity may be favoured by the location of the electrode in the ventral part of the STN.

Postoperative empyema following chronic subdural hematoma surgery: Clinically based medicine.

INTRODUCTION: Subdural empyema (SDE) is a rare complication of chronic subdural hematoma (CSDH) surgery. We introduced antibiotic prophylaxis (AP) for this procedure in 2014 following a morbidity-mortality conference (MMC) in our department. We report the results of retrospective data analysis to assess the effect of systematic AP and to identify risk factors for SDE. MATERIAL AND METHODS: Two hundred eight patients were recruited between January 2013 and December 2015; 5 were excluded for incomplete data: 107 without and 96 with AP (n=203). SDE was confirmed by clinical examination, imaging and bacteriological analysis. Comparisons between AP-(no cefuroxime) and AP+ (cefuroxime) groups were made with Chi2 test and Student's t-test. RESULTS: One empyema was found in each group, indicating that AP had no effect (P=1). The only criterion associated with SDE for these two patients was a greater number of reoperations for CSDH recurrence (P=0.013). DISCUSSION: The incidence of postoperative empyema was 1%, similar to the range of 0.2%-2.1% reported in the literature. This rare incidence explains why we found no significant effect of AP. The medical decision taken at the MMC did not help to reduce the rate of postoperative SDE. MMCs can help to define factors associated with adverse surgical events and identify opportunities for improvement. CONCLUSION: AP, introduced after an MMC, did not impact SDE rates. In practice, AP should be required only in case of reoperation for CSDH recurrence. However, we still continue to use AP following the MMC considering different parameters discussed in the manuscript.

Assessment of Maturational Changes in White Matter Anisotropy and Volume in Children: A DTI Study.

BACKGROUND AND PURPOSE: Anisotropy is a good indicator of white matter fascicle macrostructure and organization but the interpretation of its changes with age remains difficult. The increase of WM fascicle fractional anisotropy with time and its relationship with WM fascicle volume have never been examined during childhood. We studied the maturation of associative WM fascicles during childhood using MR imaging-based DTI. We explored whether the fractional anisotropy increase of the main WM fascicles persists beyond the period of brain growth and is related to WM fascicle volume increase. MATERIALS AND METHODS: In a series of 25 healthy children, the fractional anisotropy and volume of 15 associative WM fascicles were calculated. Several regression linear mixed models were used to study maturation parameters (fractional anisotropy, volume, and total telencephalon volume) considered as dependent variables, while age and sex were independent variables (the variable identifying the different WM fascicles was considered as a repeated measure). RESULTS: In children older than 8 years of age, WM fascicle fractional anisotropy increased with age (P value = .045) but not its volume (P value = .7) or the telencephalon volume (P value = .16). The time course of WM fascicle fractional anisotropy and volume suggested that each WM fascicle might follow a specific pattern of maturation. CONCLUSIONS: The fractional anisotropy increase of several WM fascicles after 8 years of age may not result from an increase in WM fascicle volume. It might be the consequence of other developmental processes such as myelination.

Long-Term Outcomes After Linac Radiosurgery for Benign Meningiomas.

AIMS: Although several studies on outcomes following stereotactic radiosurgery (SRS) for benign meningiomas have been reported, Linac-based SRS outcomes have not been as widely evaluated. The aim of this retrospective institutional single-centre study was to determine long-term outcomes of Linac-based SRS for benign intracranial meningiomas. MATERIALS AND METHODS: From July 1996 to May 2011, 60 patients with 69 benign meningiomas were included. All patients were treated with single-fraction Linac-based SRS with four to five non-coplanar arcs, dynamic or not. The marginal dose prescribed for the periphery was 16 Gy. Prognostic factors associated with local control, progression-free survival (PFS) and overall survival were tested. RESULTS: The median follow-up was 128 months. No patient was lost to follow-up. The values observed at 1, 5 and 10 years were, respectively, 100%, 98.4% and 92.6% for local control, 94.9%, 93.2% and 78% for PFS and 100%, 94.7% and 92.7% for overall survival. In univariate analysis, local control after SRS was significantly higher for skull base and parasagittal meningiomas compared with convexity meningiomas (P = 0.031). Multivariate analyses showed significantly longer PFS when the minimum dose delivered to the tumour was greater than 10 Gy (P = 0.0082). No grade 5 toxicity was reported. CONCLUSION: Our long-term results from a large sample size of benign meningiomas treated with Linac-based SRS confirmed excellent local control (>90%) and good safety, which is in line with published studies on Gamma Knife surgery. Above all, we showed significantly poorer PFS if the minimum dose to the tumour was under 10 Gy.

[Functional stereotactic radiosurgery: Indications and perspectives]. / Radiochirurgie fonctionnelle : indications et perspectives.

Stereotactic radiosurgery (SRS) is a non-invasive technique that enables to create brain focal lesions with a high precision and localization. Thus, functional brain disorders can be treated by SRS in case of pharmacoresistance or inoperability. To date, treatment of trigeminal neuralgia is the most described and known indication. Other indications will be developed in the future like movement disorders, refractory epilepsy, obsessive compulsive disorder and severe depression. We present here a review of actual and future indications of functional brain SRS with their level of evidence. All these SRS treatments have to be strictly conducted by trained teams with an excellent collaboration between radiation physicists, medical physicists, neurosurgeons, neurologists, psychiatrists and probably neuroradiologists.

Cadmium-Induced Renal Cell Toxicity Is Associated With MicroRNA Deregulation.

Cadmium is an environmental pollutant well known for its nephrotoxic effects. Nevertheless, mechanisms underlying nephrotoxicity continue to be elucidated. MicroRNAs (miRNAs) have emerged in recent years as modulators of xenobiotic-induced toxicity. In this context, our study aimed at elucidating whether miRNAs are involved in renal proximal tubular toxicity induced by cadmium exposure. We showed that cadmium exposure, in 2 distinct renal proximal tubular cell models (renal proximal tubular epithelial cell [RPTEC]/human telomerase reverse transcriptase [hTERT] and human kidney-2), resulted in cytotoxicity associated with morphological changes, overexpression of renal injury markers, and induction of apoptosis and inflammation processes. Cadmium exposure also resulted in miRNA modulation, including the significant upregulation of 38 miRNAs in RPTEC/hTERT cells. Most of these miRNAs are known to target genes whose coding proteins are involved in oxidative stress, inflammation, and apoptosis, leading to tissue remodeling. In conclusion, this study provides a list of dysregulated miRNAs which may play a role in the pathophysiology of cadmium-induced kidney damages and highlights promising cadmium molecular biomarkers that warrants to be further evaluated.

Environmental scenarii for the degradation of oxo-polymers.

The fate of oxo-polymers in nature is strongly dependent on environmental conditions, mainly on the intensity and duration of sunshine, which vary with the season and the climate. In this work, we report the effect of different scenarii on the production and the molecular composition of oligomers released from oxo-biodegradable HDPE films. Under our experimental conditions, the duration of accelerated weathering corresponded to a period of 3 months to 3 years of exposure to outside conditions under temperate climate. In addition, the oligomers were extracted in three different solvents: i) water to mimics the natural environment; ii) acetone and chloroform to identify oligomers trapped in the polymer matrix. The combination of high-resolution mass spectrometry and 1H NMR spectroscopy gives an extensive picture of the relative concentrations and the structural compositions of the extracted oligomers in the different tested conditions. In particular, the masses, the number of oxygen and carbon atoms could be determined for up to 2283 molecules. Globally the concentration and the size of oligomers increased with the duration of extraction, the level of aging of the polymer and the use of non-polar solvents. Surprisingly, the presence of highly oxidized molecules in acetone and chloroform extract, suggested an important swelling of HPDE films in these solvents and a better diffusion of these oligomers in the matrix. In nature, the biodegradability of oligomers could result from processes occurring both at the molecular (oxidation) and the macromolecular (diffusion and release) levels.

Fractionated radiotherapy and radiosurgery of intracranial meningiomas.

This review focuses on the role of radiosurgery and fractionated radiotherapy in the management of intracranial meningiomas, which are the most common benign intracranial tumors. Whenever feasible, surgery remains a cornerstone of treatment in effective health care treatment where modern radiotherapy plays an important role. Irradiation can be proposed as first-line treatment, as adjuvant treatment, or as a second-line treatment after recurrence. Stereotactic radiosurgery consists of delivering, a high-dose of radiation with high precision, to the tumor in a single-fraction with a minimal exposure of surrounding healthy tissue. Stereotactic radiosurgery, especially with the gamma knife technique, has reached a high level of success for the treatment of intracranial meningiomas with excellent local control and low morbidity. However, stereotactic radiosurgery is limited by tumor size,<3-4cm, and location, i.e. reasonable distance from the organs at risk. Fractionated radiation therapy is an interesting alternative (5 to 6weeks treatment time) for large inoperable tumors. The results of fractionated radiation therapy seem encouraging as regards both local control and morbidity although long-term prospective studies are still needed.

Characterization of oxidized oligomers from polyethylene films by mass spectrometry and NMR spectroscopy before and after biodegradation by a Rhodococcus rhodochrous strain.

The objective of this work was to develop a new approach to assess the specificity and the efficiency of biodegradation of oxidized oligomers extracted from aged HDPE polyethylene films and to bring insight on the mechanisms occurring during biodegradation. 1H NMR spectroscopy and LC Orbitrap™ mass spectrometry were combined together with data processing using Kendrick mass defect calculation and Van Krevelen Diagram. We showed that the molecular weight of extracted oligomers was lower than 850 Da with maximum chain length of 55 carbon atoms. The oligomers were divided into 11 classes of molecules with different oxidation state ranging from 0 to 10. All classes included series of chemically related compounds including up to 19 molecules. 95% of the soluble oligomers were assimilated by a strain of Rhodococcus rhodocchrous after 240 days of incubation. Large highly oxidized molecules completely disappeared while the other classes of molecules were still represented. Molecules containing 0-1 oxygen atom were less degraded. A strong shift to smaller molecules (<450 Da, 25 carbon atoms) was observed suggesting that longer molecules disappeared more rapidly than the smaller ones. It opens new perspectives on biodegradation processes as not only intracellular ß-oxidation must be considered but also extracellular mechanisms leading to chain cleavages.

Surgery for massive splenomegaly.

BACKGROUND: Splenectomy for massive splenomegaly (spleen weight more than 1·5 kg) is commonly believed to be hazardous and to provide poor palliation. The aim of this cohort study was to investigate these issues and examine the many definitions of massive splenomegaly to see whether a better tool might be proposed for preoperative evaluation of these patients. METHODS: Morbidity and long-term outcomes were assessed in consecutive patients. Relief of pressure-volume-related symptoms and sustainable independence from transfusion in patients were used to ascertain the impact of splenectomy. RESULTS: Splenectomy was performed in 56 patients, mainly for non-Hodgkin's lymphoma and myeloproliferative diseases. Median spleen weight was 2·3 (range 1·5-6·0) kg. Mortality at 180 days was zero, and the postoperative complication rate was 25 per cent (17 complications in 14 patients). At 2 years, relief of pain was maintained in 33 of 34 patients, with sustained independence from transfusion in 15 of 19 patients with anaemia and nine of 11 with thrombocytopenia. Spleen weight correlated negatively with BMI (P = 0·036). CONCLUSION: Splenectomy for massive splenomegaly is safe and provides effective palliation. Provisional cut-off points relating to spleen size and BMI help to identify patients benefiting from a splenectomy, even those in a critical state.

Personalized mapping of the deep brain with a white matter attenuated inversion recovery (WAIR) sequence at 1.5-tesla: Experience based on a series of 156 patients.

OBJECTIVE: Deep brain mapping has been proposed for direct targeting in stereotactic functional surgery, aiming to personalize electrode implantation according to individual MRI anatomy without atlas or statistical template. We report our clinical experience of direct targeting in a series of 156 patients operated on using a dedicated Inversion Recovery Turbo Spin Echo sequence at 1.5-tesla, called White Matter Attenuated Inversion Recovery (WAIR). METHODS: After manual contouring of all pertinent structures and 3D planning of trajectories, 312 DBS electrodes were implanted. Detailed anatomy of close neighbouring structures, whether gray nuclei or white matter regions, was identified during each planning procedure. We gathered the experience of these 312 deep brain mappings and elaborated consistent procedures of anatomical MRI mapping for pallidal, subthalamic and ventral thalamic regions. We studied the number of times the central track anatomically optimized was selected for implantation of definitive electrodes. RESULTS: WAIR sequence provided high-quality images of most common functional targets, successfully used for pure direct stereotactic targeting: the central track corresponding to the optimized primary anatomical trajectory was chosen for implantation of definitive electrodes in 90.38%. CONCLUSION: WAIR sequence is anatomically reliable, enabling precise deep brain mapping and direct stereotactic targeting under routine clinical conditions.

Relearning of Activities of Daily Living: A Comparison of the Effectiveness of Three Learning Methods in Patients with Dementia of the Alzheimer Type.

This study examined the effectiveness of three different learning methods: trial and error learning (TE), errorless learning (EL) and learning by modeling with spaced retrieval (MR) on the relearning process of IADL in mild-to-moderately severe Alzheimer's Dementia (AD) patients (n=52), using a 6-weeks randomized controlled trial design. The participants had to relearn three IADLs. Repeated-measure analyses during pre-intervention, post-intervention and 1-month delayed sessions were performed. All three learning methods were found to have similar efficiency. However, the intervention produced greater improvements in the actual performance of the IADL tasks than on their explicit knowledge. This study confirms that the relearning of IADL is possible with AD patients through individualized interventions, and that the improvements can be maintained even after the intervention.

Impact of localisation of deep brain stimulation electrodes on motor and neurobehavioural outcomes in Parkinson's disease.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) represents a well-established treatment in advanced Parkinson's disease (PD) for motor signs, but it is still debated concerning psychiatric effects. OBJECTIVE: Exploration of relation between position of active electrode contacts and neuropsychological and motor change after STN DBS procedure for PD. METHODS: A cohort of 34 patients who underwent STN DBS was followed for 6 months. Preoperative and postoperative assessments included mood evaluation (depression and mania) and motor status. Active contact localisation was identified regarding position into the STN (4 groups: IN meant contacts were IN-IN IN-BORDER; OUT: OUT-OUT or OUT-BORDER; BORDER: BORDER-BORDER; IN-OUT: IN-OUT) and compared with clinical outcomes. RESULTS: STN DBS significantly improved motor scores and reduced dopaminergic medication when compared with baseline and active lead groups: the best result was seen with the IN group. At 3 and 6 months postsurgery, depression and manic scores do not significantly differ compared with baseline and between leads groups. Focusing on symptom domains and compared with baseline, a significant loss of appetite was observed for the IN group at M3 and a significant increase in appetite from baseline was observed at M3 for the OUT group. Graphic representations illustrate that postsurgery evolution parameters at M3 or M6 are very good discriminant variables and well differentiate all leading groups. CONCLUSIONS: Stimulation of zona incerta may influence appetite and weight gain. Our clinical results seem to support a personalised DBS-targeted Parkinson therapy including individual motor and non-motor parameters.

[Intra cranial meningiomas and long term use of cyproterone acetate with a conventional dose in women. A report of two cases of tumor decrease after treatment withdrawal]. / Méningiomes intracrâniens et utilisation prolongée d'acétate de cyprotérone à dose conventionnelle chez la femme: à propos de deux cas de régression tumorale après arrêt du traitement.

The action of synthetic progestogens, prescribed at a conventional dose in women, for a meningioma, is still poorly understood, and could be related to progesterone receptors. We report two cases illustrating multiple meningiomas with stabilization or tumor reduction after withdrawal of cyproterone acetate originally prescribed for a long term period. We also review the influence of synthetic progestogens on meningiomas, particularly the impact of treatment withdrawal.

Incidence and survival of childhood central nervous system tumors: A report of the regional registry of childhood cancers in Auvergne-Limousin.

INTRODUCTION: Central nervous system tumors (CNST) are the most lethal of solid tumors in childhood cancer. PATIENTS AND METHODS: We report incidence and survival data for all CNST (International Classification of Diseases for Oncology third edition, category III or Xa) recorded in children under 15 years of age by the Auvergne-Limousin cancer registry for the period 1986-2009. RESULTS: Annual incidence of all CNST was 3.27 per 100,000 and the male to female ratio was 0.95. Over 45.0% of CNST were glial. Astrocytomas (36.2%) showed the highest incidence for each age group except between 1 and 4 years where embryonal tumors were more common. For all CNST, no significant variation in incidence over time was observed for the evaluated period of 23 years (annual percent change: -0.4%, 95% CI, [-2.8-2.1]). Globally, 5 years overall survival was 67% [59-73] and had increased by more than 16% between 1986-1999 and 2000-2009, mainly due to better survival for astrocytomas, other gliomas, ependymomas and choroid plexus tumors (P=0.01). CONCLUSION: We report that the incidence of CNST in Auvergne-Limousin is similar to that in the literature and did not increase between 1986 and 2009. In addition, 5 years overall survival increased after 1999, especially for surgically treatable tumors.

[Medico-economic analysis of a neurosurgery department at a university hospital]. / Analyse médico-économique d'un service de neurochirurgie en centre hospitalier et universitaire.

OBJECTIVE: Economic and societal constraints require to take into account the economic dimension and medical performance of hospital departments. We carried out a self-assessment study, which we thought could be useful to share with the neurosurgical community. MATERIAL AND METHODS: Care and research activities were assessed from 2009 to 2013. We used institutional and assessment-body parameters in order to describe activities and perform a financial evaluation. It was a retrospective descriptive study based on the guidelines of the DHOS/O4 circular No. 2007/390 of October 29, 2007. RESULTS: The average annual, analytic income statement was +1.39 millions euros, for 63 beds with a 92% occupancy rate, including 6.7 full-time equivalent neurosurgeons (and assistants), for 2553 patients and 1975 surgeries. The average mortality rate was 2.74%. The annual mean length of stay was 6.82 days. Per year, on average 15.6% of patients were admitted in emergency and 76.9% returned home. The annual, act-related-pricing and publication-related incomes represented 77% and 0.6%, respectively of the total funding. Difficulties to find downstream beds for the most severe patients induced 1401 "waiting days" in 2012. CONCLUSION: Medico-economic analysis of a neurosurgery department at a university hospital was useful in order to take into account the care, teaching and research activities, as well as its related financial value.