Effect of meditation on intracerebral EEG in a patient with temporal lobe epilepsy: A case report.

Meditation has been deemed a miracle cure for a wide range of neurological disorders. However, it is unclear whether meditation practice would be beneficial for patients suffering from epilepsy. Here we report on the comparison of the effects of focused-attention meditation and a control task on electroencephalographic (EEG) activity in a patient undergoing stereoencephalographic (SEEG) investigation for drug-resistant epilepsy. The patient routinely practiced focused-attention meditation and reported that she found it beneficial. During the SEEG investigation, intracerebral EEG data were recorded during meditation as well as during mind-wandering task. The EEG data were analyzed for type of electrical activity (labeled) by two expert epileptologists. We found that the proportion of EEG segments containing activity classified as interictal epileptiform discharges (IEDs; abnormal electrical activity that occurs between seizures) increased significantly during meditation practice. Although the finding was surprising, this increase in IEDs may not correlate with an increase in seizure frequency, and the patient might still benefit from practicing meditation. The finding does, however, warrant further studies on the influence of meditation on epileptic activity.

[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.

Micropatterned bioimplant with guided neuronal cells to promote tissue reconstruction and improve functional recovery after primary motor cortex insult.

With the ever increasing incidence of brain injury, developing new tissue engineering strategies to promote neural tissue regeneration is an enormous challenge. The goal of this study was to design and evaluate an implantable scaffold capable of directing neurite and axonal growth for neuronal brain tissue regeneration. We have previously shown in cell culture conditions that engineered micropatterned PDMS surface with straight microchannels allow directed neurite growth without perturbing cell differentiation and neurite outgrowth. In this study, the micropatterned PDMS device pre-seeded with hNT2 neuronal cells were implanted in rat model of primary motor cortex lesion which induced a strong motor deficit. Functional recovery was assessed by the forelimb grip strength test during 3 months post implantation. Results show a more rapid and efficient motor recovery with the hNT2 neuroimplants associated with an increase of neuronal tissue reconstruction and cell survival. This improvement is also hastened when compared to a direct cell graft of ten times more cells. Histological analyses showed that the implant remained structurally intact and we did not see any evidence of inflammatory reaction. In conclusion, PDMS bioimplants with guided neuronal cells seem to be a promising approach for supporting neural tissue reconstruction after central brain injury.

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.

Bilateral ophthalmic origin of the middle meningeal artery.

The origin of the middle meningeal artery (MMA) may vary although it can arise from the ophthalmic artery (OA) with a 0.5% prevalence. We report the exceptional bilateral asymmetric origin from the OAs that has not previously been reported in the literature. Surgeons should be aware of this variation as it could be crucial in the setting of an endovascular approach for meningeal lesions, as in our observation. A 50-year-old male underwent a preoperative cerebral digital subtracted angiography that incidentally revealed MMAs arising from the OA on both sides. In fact, the origin was asymmetric because it was complete on the right side with the anterior and posterior branches of the MMA arising from the OA, whereas it was partial on the left side, with only the anterior branch arising from the OA. The CT scan showed the absence of the foramen spinosum only on the right side. This paper discusses the unique anatomic variation in the light of MMA embryology and its different origins. Knowledge of this variation may have a practical impact in cases of cerebral embolization.

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.

Adult human progenitor cells from the temporal lobe: another source of neuronal cells.

OBJECTIVES: In the adult human brain, neurogenesis occurs in the SVZ and the dentate gyrus of the hippocampus, but it is still unclear whether persistent neural progenitor/stem cells are also present in other brain areas. The present work studies the possibility of obtaining neural progenitor/stem cells from the temporal lobe and investigates their potential to differentiate into neuronal cells. METHODS: Human biopsies from the temporal lobe of epileptic patients were used to isolate potential neural progenitors. Differentiation was induced in the presence of different agents (NGF, NT3, RA) and immunocytochemistry was then performed for quantitative analysis. RESULTS: It was shown that a significant number of cells in the temporal lobe are also capable of expansion and multi-potency. These cells can be amplified as neurospheres and have the potential to differentiate naturally in vitro into neurons, astrocytes and oligodendrocytes. Quantitative analyses show that the progenitor cells of the temporal lobe exhibit a better rate of neuronal differentiation in vitro than the cells from the SVZ, particularly in the presence of NGF. CONCLUSION: This study indicates that neural progenitors are also present in the human temporal lobe. Studying them could be of great interest for cell therapy in neurological disorders.

[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.

GABAergic pathway in a rat model of chronic neuropathic pain: modulation after intrathecal transplantation of a human neuronal cell line.

Current understanding of chronic pain points a decrease in level of the inhibitory neurotransmitter GABA, in the spinal dorsal horn, leading to an imbalance between excitatory and inhibitory pathways. A subcloned derivative of the human NT2 cell line (hNT2.17) which, after neuronal differentiation, secretes different inhibitory neurotransmitters such as GABA and glycine has been recently isolated. In this study, we have investigated the effect of this new cell line on peripheral nerve injury induced by chronic constriction (CCI) and notably the effect on the cellular GABAergic pathway. Our data show that the decrease in GABA expression in the spinal dorsal horn of injured animals is concomitant with a decline of its synthetic enzyme GAD67-Ir and mRNA but not GAD65. Interestingly, in transplanted animals we observed a strong induction of GAD67 mRNA with one week after graft, which is followed by a recovery of GAD67 and GABA Ir. This effect paralleled a reduction of hindpaw hypersensitivity and thermal hyperalgesia induced by CCI. These results suggest that hNT2.17 GABA cells can modulate neuropathic pain after CCI certainly by minimizing the imbalance and restoring the cellular GABAergic pathway.

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.

Motor cortex stimulation for neuropathic pain.

Since the initial publication of Tsubokawa in 1991, epidural motor cortex stimulation (MCS) is increasingly reported as an effective surgical option for the treatment of refractory neuropathic pain although its mechanism of action remains poorly understood. The authors review the extensive literature published over the last 15 years on central and neuropathic pain. Optimal patient selection remains difficult and the value of pharmacological tests or transcranial magnetic stimulation in predicting the efficacy of MCS has not been established. Pre-operative functional magnetic resonance imaging (fMRI), 3-dimensional volume MRI, neuronavigation and intra-operative neurophysiological monitoring have contributed to improvements in the technique for identifying the precise location of the targeted motor cortical area and the correct placement of the electrode array. MCS should be considered as the treatment of choice in post-stroke pain, thalamic pain or facial anesthesia dolorosa. In brachial plexus avulsion pain, it is preferable to propose initially dorsal root entry zone (DREZ)-tomy; MCS may be offered after DREZotomy has failed to control the pain. In our experience, the results of MCS on phantom limb pain are promising. In general, the efficacy of MCS depends on: a) the accurate placement of the stimulation electrode over the appropriate area of the motor cortex, and b) on sophisticated programming of the stimulation parameters. A better understanding of the MCS mechanism of action will probably make it possible to adjust better the stimulation parameters. The conclusions of multicentered randomised studies, now in progress, will be very useful and are likely to promote further research and clinical applications in this field.

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.

[Self-assessment for neurosurgery residents by script concordance test (SCT). The process of test elaboration]. / Auto-évaluation des internes en neurochirurgie par tests de concordance de script (TCS). Processus d'élaboration des tests.

BACKGROUND: The script concordance test (SCT) is a new tool to assess clinical reasoning in a context of uncertainty. It was chosen for computer-based self-assessment training for neurosurgery residents. PURPOSE: The aim of this work is to describe the construction of a first series of questions and provide teachers practical information needed to build a SCT. METHOD: The theorical background of the SCT is explained. We review the steps we followed when writing of a series of more than two hundred questions. RESULTS: We present the different steps of our work, including writing clinical cases, validation of questions and elaboration of scoring systems. We explain the main difficulties we encountered. CONCLUSION: The script concordance test is an interesting easy-to-construct assessment tool useful for evaluating clinical competence. This work summarizes our experience in building a SCT, which should be helpful for teachers interested in this new assessment tool, especially in neurosurgery.

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.