[Treatment of patients with brain metastases from a melanoma]. / Prise en charge des patients atteints de métastases cérébrales de mélanome.

Whereas immune checkpoint inhibitors of serine/threonine protein kinase B-raf therapy dramatically changed metastatic outcomes of patients with melanoma, they remain at high risk of brain extension. Additional local treatment can be offered in this situation such as surgery and or stereotactic radiotherapy. In this review article, we describe the different options with published data and their optimal timing.

Cervical laminectomy and micro resection of the posterior venous plexus in Hirayama disease.

INTRODUCTION: Hirayama disease is a rare cervical myelopathy predominantly affecting young adults and mainly found in Asia. It results in a pure motor distal lesion of the upper limbs with slow progression. Dynamic magnetic resonance imaging (MRI), which allows the diagnosis to be made, shows a typical appearance of anterior compression of the cervical spinal cord associated with enlargement of the posterior epidural spaces due to a dilated venous plexus. Surgery is considered when conservative treatment has failed. However, the type of surgery is not well standardized in this compressive myelopathy. METHODS: We report on three patients with Hirayama disease operated using an original method: cervical decompressive laminectomy and coagulation of the posterior epidural plexus without fixation. The clinical, radiological and surgical data of these three patients were analyzed. Each patient underwent postoperative MR imaging. RESULTS: The mean age at diagnosis was 18.6 years (16-20 years) with a history of progressive symptoms lasting 1 to 4 years before treatment. Follow-up was 21 to 66 months after surgery. Neurological and electrophysiological improvement was noted in two patients; the third had stabilized. Postoperative MRI confirmed normalization of flexion imaging on MRI. None of the three patients complained of disabling neck pain. CONCLUSION: Posterior cervical decompression with coagulation of epidural venous plexus is a technique that seems effective in Hirayama disease in young subjects. It effectively treats patients by avoiding permanent cervical fixation.

Subventricular zone involvement at recurrence is a strong predictive factor of outcome following high grade glioma reirradiation.

We aimed to assess the efficacy of stereotactic irradiation for patients with recurrent high-grade glioma (HGG) and identify predictive factors of progression-free survival (PFS) and overall survival (OS) following reirradiation. We identified 32 patients with recurrent brain HGG who had been treated with either single-dose (stereotactic radiosurgery) or fractionated stereotactic radiotherapy between April 2008 and October 2015. Median follow up was 21.4 months (range 12.9-23.2) and median PFS was and 3.3 months (95% CI [2.3-4.7]), respectively. OS was 90.40% (95% CI [73.09-96.80]) at 6 months and 79.55% (95% CI [59.9-90.29]) at 12 months. Univariate analysis showed that biological effective dose at isocenter ≤ 76 Gy was a poor prognostic factor for both OS (83.33 vs. 100% at 6 months, p = 0.032) and median PFS (2.7 vs. 4.7 months, p = 0.025), as was gross tumor volume (GTV) above 1 cm3 for OS (86.15 vs. 94.12% at 6 months, p = 0.043). Contact with the subventricular zone (SVZ) was also a poor prognostic factor for median PFS (2.3 vs. 4.7 months, p = 0.002). Multivariate analysis showed that SVZ contact remained a poor prognostic factor for PFS (hazard ratio = 3.44, 95% CI [1.21-9.82], p = 0.021). Results suggest that reirradiation is a safe and effective treatment option for recurrent HGG in patients with a good Karnosfsky Performance Scale score, a long progression-free interval since first radiation and limited GTV, and that contact to SVZ is a strong prognostic factor for PFS.

Children's outcomes at 2-year follow-up after 4 years of structured multi-professional medical-ethical decision-making in a neonatal intensive care unit.

OBJECTIVE: We reviewed our decisions about continuation/withdrawal of life-sustaining treatments in a group of critically ill newborns who were discussed in structured medical ethical decision-making meetings, and provide the surviving children's outcomes at 2-year follow-up. STUDY DESIGN: In an explorative observational study, 61 cases were evaluated. The children involved had been discussed in such a structured way from 2009 to 2012 in a level III-D neonatal intensive care unit. RESULTS: Decisions made were: full treatment (n=6), earlier restriction cancelled (n=3), treatment restriction (n=30) and palliative care (n=22). Parents of six children disagreed with the decision proposed. Thirteen (54%) of the 24 children who survived (39%) had moderate to severe neurological problems; 8 (33%) had additional sequelae; only one 2-year-old child was healthy. CONCLUSIONS: Decisions made varied to a large extent. The poor outcomes should be disseminated among decision makers. Future studies must explore new ways to improve outcome prediction, extend follow-up periods and consider what living with severe handicaps really means for both child and family.

Prognostic Value of Modified Banff Score in the Evolution of Renal Function.

BACKGROUND: Some lesions not included in the Banff classification, such as inflammation in the scarred areas and total inflammation, have been described to have prognostic value in the evaluation of graft biopsies. Our aim was to reassess kidney graft biopsies and study the impact of histopathologic lesions, both those graded in the Banff classification and those related to inflammation, on the graft function and evolution. METHODS: We selected 20 biopsies exhibiting chronic pathology without a specific phenotype, and we reevaluated them with the use of a modified Banff score. RESULTS: We found statistically significant association between the presence of total inflammation (P = .048; P = .038), the presence of inflammation in scared area (P = .037; P = .018), and creatinine at the time of renal biopsy and 1 year after the renal biopsy, respectively. CONCLUSIONS: Our results suggest that the presence of both inflammation in the scarred areas and total inflammation are related to renal function at the time of the biopsy and to renal function 1 year after the biopsy.

Multicolumn spinal cord stimulation for significant low back pain in failed back surgery syndrome: design of a national, multicentre, randomized, controlled health economics trial (ESTIMET Study).

BACKGROUND: Many studies have demonstrated the efficacy of spinal cord stimulation (SCS) for chronic neuropathic radicular pain over recent decades, but despite global favourable outcomes in failed back surgery syndrome (FBSS) with leg pain, the back pain component remains poorly controlled by neurostimulation. Technological and scientific progress has led to the development of new SCS leads, comprising a multicolumn design and a greater number of contacts. The efficacy of multicolumn SCS lead configurations for the treatment of the back pain component of FBSS has recently been suggested by pilot studies. However, a randomized controlled trial must be conducted to confirm the efficacy of new generation multicolumn SCS. Évaluation médico-économique de la STImulation MEdullaire mulTi-colonnes (ESTIMET) is a multicentre, randomized study designed to compare the clinical efficacy and health economics aspects of mono- vs. multicolumn SCS lead programming in FBSS patients with radicular pain and significant back pain. MATERIALS AND METHODS: FBSS patients with a radicular pain VAS score≥50mm, associated with a significant back pain component were recruited in 14 centres in France and implanted with multicolumn SCS. Before the lead implantation procedure, they were 1:1 randomized to monocolumn SCS (group 1) or multicolumn SCS (group 2). Programming was performed using only one column for group 1 and full use of the 3 columns for group 2. Outcome assessment was performed at baseline (pre-implantation), and 1, 3, 6 and 12months post-implantation. The primary outcome measure was a reduction of the severity of low back pain (bVAS reduction≥50%) at the 6-month visit. Additional outcome measures were changes in global pain, leg pain, paraesthesia coverage mapping, functional capacities, quality of life, neuropsychological aspects, patient satisfaction and healthcare resource consumption. TRIAL STATUS: Trial recruitment started in May 2012. As of September 2013, all 14 study centres have been initiated and 112/115 patients have been enrolled. Preliminary results are expected to be published in 2015. TRIAL REGISTRATION: Clinical trial registration information-URL: www.clinicaltrials.gov. Unique identifier NCT01628237.

A prospective video-based observational and analytical approach to evaluate management during brain tumour surgery at a university hospital.

The operating room (OR) is a high-risk complex setting, where patient safety relies on the coordinated efforts of multiple team members. However, little attention has been paid to evaluating the strategies employed by OR practitioners to prevent and correct incidents that inevitably occur during surgery. Therefore, we were prompted to investigate human factor (HF) engineering methods that have been used in an innovative way in order to systematically observe and analyze the management of incidents in the neurosurgical OR of a French university hospital. A technical case report illustrates our approach that associates the following procedures: the recording of OR team member activities and behaviour by video cameras and direct observation of a HF researcher, with the description and the explicit demonstration of safety related procedures in self- and cross-confrontation interviews of OR team members. This technical report emphasizes complementary aspects of clinical performance related to safety skills. Moreover, individual and team performances rely on complementary abilities that associate practical knowledge, skills, and attitudes, which are engaged at various degrees to prevent and manage incidents. This report also enlightens new quality-improvement opportunities as well as further objectives for future studies.

[Treatment of trigeminal neuralgia with radiosurgery]. / Traitement de la névralgie essentielle du trijumeau par radiochirurgie stéréotaxique.

Idiopathic trigeminal neuralgia is defined as brief paroxysms of pain limited to the facial distribution of the trigeminal nerve. Drug therapy is considered to be the first-line of treatment for trigeminal neuralgia. Unfortunately, medical treatment does not always provide satisfactory pain relief for 25% of the patients. Moreover, the relief provided by drug therapy generally decreases over time, and increased dosages of these medications are limited because of side effects. In this case, patients can be offered several surgical approaches, such as percutaneous techniques (thermocoagulation, microcompression, glycerol injection) or microvascular decompression in the cerebello-pontine angle (Gardner-Jannetta's technique). In this indication, stereotactic radiosurgery, driven by teams using Gamma Knife(®), has shown promising efficacy and tolerance to allow this treatment being truly part of trigeminal neuralgia treatment. Technological progresses now allow performing radiosurgery with ballistic and dosimetric processes optimized with stereotactic radiosurgery dedicated linear accelerators. This procedure supports frame implantation to guarantee targeting accuracy in accordance of elevated dose distribution. This article on trigeminal neuralgia treatment will review the different medical and surgical therapeutic options and specify the contemporary place of stereotactic radiosurgery in the light of its clinical results and tolerance aspects.

[Review of the target for the deep brain stimulation of chronic cluster headache]. / Revision de la diana para la estimulacion cerebral profunda de la cefalea en racimos cronica.

Cluster headache is included in the group of trigeminal autonomic cephalalgias. Although the pathophysiology of cluster headache has not yet been sufficiently established, the theory of a central origin tells us that this headache is produced by hypothalamic dysfunction. More than 50 patients have been treated with deep brain stimulation of the posterior nucleus of the hypothalamus from 2001. The results show clinical improvement in more than 60% of the cases, opening a promising issue for the treatment of the cluster headache persistent after medical treatment. The surgical target that have been used until now is based on the origin of the cluster headache in the hypothalamic dysfunction. Nevertheless, It has still some open questions as the lack of proving the posterior nucleus of the hypothalamus is the real origin of the cluster headache, the lack of consensus about the anatomy of the surgical target and the variability of the structures stimulated with the surgery. The aim of this article is a review of the target used and propose another surgical target based on physiopathological concepts to explain the improvement with the deep brain stimulation in these patients.

Patients' experiences and preferences with co-managed care in a cataract pathway.

BACKGROUND/AIMS: Co-managed care in cataract pathways allows ophthalmologists more time to treat other patients. However, little is known on how patients experience pathways that greatly reduce the amount of time spent with ophthalmologists. PURPOSE: To determine experiences and preferences of cataract patients with co-managed postoperative care. METHODS: In a nested-case control study, 194 patients who received their first-day review and final review by an ophthalmologist and 289 patients who received a telephone first-day review by a nurse and a final review by an optometrist were included. The Consumer Quality Index Cataract Questionnaire was used to measure patients' experiences with the quality of care after uncomplicated first-eye cataract surgery. RESULTS: Patients in the co-managed care pathway reported similarly good experiences with the quality of care as patients who received their reviews by an ophthalmologist. Patients who were reviewed by a nurse reported to prefer the same first-day review method significantly more often than those who were reviewed by an ophthalmologist. Most patients preferred the final review by an ophthalmologist. CONCLUSION: Overall, patients with cataract highly rated co-managed care pathways without any postoperative contact with ophthalmologists. Nevertheless, patients still preferred ophthalmologists for their final review to optometrists. Any added patients' benefits should be clearly determined before substituting activities from ophthalmologists to other care professionals.

[Epilepsy surgery in France]. / La chirurgie de l'épilepsie en France Evaluation de l'activité

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

Viability and functionality of bovine chromaffin cells encapsulated into alginate-PLL microcapsules with a liquefied inner core.

Implantation of adrenal medullary bovine chromaffin cells (BCC), which synthesize and secrete a combination of pain-reducing neuroactive compounds including catecholamines and opioid peptides, has been proposed for the treatment of intractable cancer pain. Macro- or microencapsulation of such cells within semipermeable membranes is expected to protect the transplant from the host's immune system. In the present study, we report the viability and functionality of BCC encapsulated into microcapsules of alginate-poly-L-lysine (PLL) with a liquefied inner core. The experiment was carried out during 44 days. Empty microcapsules were characterized in terms of morphology, permeability, and mechanical resistance. At the same time, the viability and functionality of both encapsulated and nonencapsulated BCC were evaluated in vitro. We obtained viable BCC with excellent functionality: immunocytochemical analysis revealed robust survival of chromaffin cells 30 days after isolation and microencapsulation. HPLC assay showed that encapsulated BCC released catecholamines basally during the time course study. Taken together, these results demonstrate that viable BCC can be successfully encapsulated into alginate-PLL microcapsules with a liquefied inner core.

Cell therapy of pain: Characterization of human fetal chromaffin cells at early adrenal medulla development.

Adult adrenal chromaffin cells are being utilized for therapeutic transplantation. With the prospect of using fetal chromaffin cells in pain therapy, we studied their phenotype, proliferative power, function, and growth in vitro and in situ in order to determine the optimal time for implantation. Between 7 and 10 gestational weeks (GW), we isolated, in vitro, two types of chromaffin cells with a noradrenergic phenotype akin to that observed, in situ. Among the adherent chromaffin cells first observed in vitro, only a few samples expressed met-enkephalin, whereas almost all the neurosphere-like colonies, which appeared later, expressed it. However, neither of the two types of populations expressed an adrenergic phenotype in line with that observed in situ. At the upper limits of the voluntary abortion period authorized in France, this phenotype (12 GW) and met-enkephalin expression (13 GW) were evidenced in situ. For the first time in man, we demonstrate the secretion of noradrenaline in vitro by the two populations of cells. Consistent with this result, we also noted dopamine beta hydroxylase (DbetaH) mRNA expression in vitro and in situ within this period. These observations on the expression of these biological factors indicate that 9-10 GW would be the best stage for sampling these cells for preclinical transplantation experiments.

Intrathecal grafting of porcine chromaffin cells reduces formalin-evoked c-Fos expression in the rat spinal cord.

Chromaffin cells from the adrenal gland secrete a combination of neuroactive compounds including catecholamines, opioid peptides, and growth factors that have strong analgesic effects, especially when administered intrathecally. Preclinical studies of intrathecal implantation with xenogeneic bovine chromaffin cells in rats have provided conflicting data with regard to analgesic effects, and recent concern over risk of prion transmission has precluded their use in human clinical trials. We previously developed a new, safer source of adult adrenal chromaffin cells of porcine origin and demonstrated an in vivo antinociceptive effect in the formalin test, a rodent model of tonic pain. The goal of the present study was to confirm porcine chromaffin cell analgesic effects at the molecular level by evaluating neural activity as reflected by spinal cord c-Fos protein expression. To this end, the expression of c-Fos in response to intraplantar formalin injection was evaluated in animals following intrathecal grafting of 10(6) porcine or bovine chromaffin cells. For the two species, adrenal chromaffin cells significantly reduced the tonic phases of the formalin response. Similarly, c-Fos-like immunoreactive neurons were markedly reduced in the dorsal horns of animals that had received injections of xenogeneic chromaffin cells. This reduction was observed in both the superficial (I-II) and deep (V-VI) lamina of the dorsal horn. The present study demonstrates that both xenogeneic porcine and bovine chromaffin cells transplanted into the spinal subarachnoid space of the rat can suppress formalin-evoked c-Fos expression equally, in parallel with suppression of nociceptive behaviors in the tonic phase of the test. These findings confirm previous reports that adrenal chromaffin cells may produce antinociception by inhibiting activation of nociceptive neurons in the spinal dorsal horn. Taken together these results support the concept that porcine chromaffin cells may offer an alternative xenogeneic cell source for transplants delivering pain-reducing neuroactive substances.

Intrathecal xenogeneic chromaffin cell grafts reduce nociceptive behavior in a rodent tonic pain model.

Adrenal medullary chromaffin cells synthetize and secrete a combination of pain-reducing neuroactive compounds including catecholamines and opioid peptides. Previous reports have shown that implantation of chromaffin cells into the spinal subarachnoid space can reduce both acute and chronic pain in several animal models. We recently demonstrated that human chromaffin cell grafts in the cerebrospinal fluid (CSF) could alleviate intractable cancer pain after failure of systemic opiates. However, wider application of this approach was limited by the limited availability of allogeneic donor material. Alternatively, chromaffin cells from xenogeneic sources such as bovine adrenal medulla were successful in the experimental treatment of pain, but recent concern over risk of prion transmission precluded use of bovine grafts in human clinical trials. The objective of the present study was to investigate the possibility of developing a new xenogeneic porcine source of therapeutic chromaffin cells because this strategy is currently considered the safest for transplantation in man. In the present study, we report the isolation and the characterization of primary porcine chromaffin cells (PCC) compared to bovine cells. We show, for the first time, that these cells grafted in the rat subarachnoid space can attenuate pain-related behaviors as assessed by the formalin test, a model of tonic pain. Moreover, in addition to behavioral studies, immunohistochemical analysis revealed robust survival of chromaffin cells 35 days after transplantation. Taken together, these results support the concept that porcine chromaffin cells may offer an alternative xenogeneic cell source for transplants delivering pain-reducing neuroactive substances.

[A case of demodicosis on a Dutch dairy farm]. / Een geval van demodicose bij Nederlands melkvee.

Demodex bovis is a burrowing mite that lives in the hair follicles of cattle, resulting in nodules, granulomatous inflammation, and the formation of scar tissue. Clinical and histopathological changes of a recently diagnosed case of demodicosis on a Dutch dairy farm are presented before and after treatment. Treatment results were disappointing. The role of demodicosis in Dutch dairy farming is discussed.

Chiari I malformation: a rare cause of noncommunicating hydrocephalus treated by third ventriculostomy.

OBJECT: Hydrocephalus associated with Chiari I malformation is a rare entity related to an obstruction in the flow of cerebrospinal fluid (CSF) in the foramen of Magendie. Like all forms of noncommunicating hydrocephalus. it can be treated by endoscopic third ventriculostomy (ETV). The object of this study is to report a series of five cases of hydrocephalus associated with Chiari I malformation and to evaluate the use of ETV in the treatment of this anomaly. METHODS: Five patients (four women and one man with a mean age of 29.6 years) underwent ETV for hydrocephalus associated with Chiari I malformation between April 1991 and February 1997. All patients had presented with paroxysmal headaches, which in two cases were associated with visual disorders. All patients had also presented with hydrocephalus (mean transverse diameter of the third ventricle 12.79 mm; mean sagittal diameter of the fourth ventricle 18.27 mm) with a mean herniation of the cerebellar tonsils at 13.75 mm below the basion-opisthion line. Surgery was performed in all patients by using a rigid endoscope. No complications occurred either during or after the procedure, except in one patient who experienced a wound infection that was treated by antibiotic medications. The mean duration of follow up in this study was 50.39 months. Four patients became completely asymptomatic and remained stable throughout the follow-up period. One patient required an additional third ventriculostomy after I year, due to secondary closure, and has remained stable since that time. Postoperative magnetic resonance images demonstrated a significant reduction in the extent of hydrocephalus in all patients (mean transverse diameter of the third ventricle 6.9 mm [p = 0.0035]; mean sagittal diameter of the fourth ventricle 10.32 mm [p = 0.007]), with a mean ascent of the cerebellar tonsils from 13.75 mm below the basion-opisthion line to 7.76 mm below it (p = 0.01). In addition, CSF flow was identified on either side of the orifice of the third ventriculostomy in all patients postoperatively. CONCLUSIONS: Results in this series confirm the efficacy of ETV in the treatment of hydrocephalus associated with Chiari I malformation. It is a reliable, minimally invasive technique that also provides a better understanding of the pathophysiology of this malformation.

Methodological and technical issues for integrating functional magnetic resonance imaging data in a neuronavigational system.

OBJECTIVE: The aim of this article was to analyze the technical and methodological issues resulting from the use of functional magnetic resonance image (fMRI) data in a frameless stereotactic device for brain tumor or pain surgery (chronic motor cortex stimulation). METHODS: A total of 32 candidates, 26 for brain tumor surgery and six chronic motor cortex stimulation, were studied by fMRI scanning (61 procedures) and intraoperative cortical brain mapping under general anesthesia. The fMRI data obtained were analyzed with the Statistical Parametric Mapping 99 software, with an initial analysis threshold corresponding to P < 0.001. Subsequently, the fMRI data were registered in a frameless stereotactic neuronavigational device and correlated to brain mapping. RESULTS: Correspondence between fMRI-activated areas and cortical mapping in primary motor areas was good in 28 patients (87%), although fMRI-activated areas were highly dependent on the choice of paradigms and analysis thresholds. Primary sensory- and secondary motor-activated areas were not correlated to cortical brain mapping. Functional mislocalization as a result of insufficient correction of the echo-planar distortion was identified in four patients (13%). Analysis thresholds (from P < 0.0001 to P < 10(-12)) more restrictive than the initial threshold (P < 0.001) had to be used in 25 of the 28 patients studied, so that fMRI motor data could be matched to cortical mapping spatial data. These analysis thresholds were not predictable preoperatively. Maximal tumor resection was accomplished in all patients with brain tumors. Chronic motor cortex electrode placement was successful in each patient (significant pain relief >50% on the visual analog pain scale). CONCLUSION: In brain tumor surgery, fMRI data are helpful in surgical planning and guiding intraoperative brain mapping. The registration of fMRI data in anatomic slices or in the frameless stereotactic neuronavigational device, however, remained a potential source of functional mislocalization. Electrode placement for chronic motor cortex stimulation is a good indication to use fMRI data registered in a neuronavigational system and could replace somatosensory evoked potentials in detection of the central sulcus.

Suprasellar seeding of a benign choroid plexus papilloma of the fourth ventricle with local recurrence.

A suprasellar location of a benign choroid plexus papilloma is reported. Local recurrence within the fourth ventricle was also present, 8 years after apparently complete removal. Imaging and histological findings were similar to those of the initial lesion. At surgery, the suprasellar lesion had no connection with the ventricular system. Seeding of choroid plexus papillomas is discussed, and the pertinent literature reviewed.