Lipidomic signature of stroke recurrence after transient ischemic attack.

While TIA patients have transient symptoms, they should not be underestimated, as they could have an underlying pathology that may lead to a subsequent stroke: stroke recurrence (SR). Previously, it has been described the involvement of lipids in different vascular diseases. The aim of the current study was to perform a lipidomic analysis to identify differences in the lipidomic profile between patients with SR and patients without. Untargeted lipidomic analysis was performed in plasma samples of 460 consecutive TIA patients recruited < 24 h after the onset of symptoms. 37 (8%) patients suffered SR at 90 days. Lipidomic profiling disclosed 7 lipid species differentially expressed between groups: 5 triacylglycerides (TG), 1 diacylglyceride (DG), and 1 alkenyl-PE (plasmalogen) [specifically, TG(56:1), TG(63:0), TG(58:2), TG(50:5), TG(53:7, DG(38:5)) and PE(P-18:0/18:2)]. 6 of these 7 lipid species belonged to the glycerolipid family and a plasmalogen, pointing to bioenergetics pathways, as well as oxidative stress response. In this context, it was proposed the PE(P-18:0/18:2) as potential biomarker of SR condition.The observed changes in lipid patterns suggest pathophysiological mechanisms associated with lipid droplets metabolism and antioxidant protection that is translated to plasma level as consequence of a more intensive or high-risk ischemic condition related to SR.

Use of a 3D virtual app and academic performance in the study of the anatomy of the musculoskeletal system among Peruvian medical students.

OBJECTIVE: To evaluate the association between the use of a 3D virtual App and academic performance among Peruvian medical students. In addition, factors associated with academic performance were also assessed. METHODS: We conducted an analytical cross-sectional study in students enrolled in the Musculoskeletal System course during the first semester of 2019. Students filled out a data collection form and the "Self-directed learning readiness scale" (SDLRS) questionnaire adapted by Fisher, King, and Tangle. Linear regression models were carried out to assess the association between the appropriate use of the application and academic performance. Additionally, the factors associated with academic performance were evaluated using nested models, and ß coefficients were calculated by manual forward selection. RESULTS: A total of 187 medical students were included. The 61% were female and the median age was 21 [20-22] years. The average grade was 13.5 ± 2 and 21% reported an adequate use of a 3D App. No association was found between the use of the 3D App and academic performance in the adjusted model (aß = 0.17; 95% CI: -0.45 to 0.80). We found that age (aß = -0.22; 95% CI: -0.39 to -0.06), performing extracurricular activities (aß = 0.75, 95% CI: 0.25 to 1.24) and having failed an anatomy/physiology course before (aß = -2.11 to 95% CI: -2.9 to -1.8) were factors associated with academic performance. CONCLUSION: The adequate use of a 3D application to study the anatomy of the musculoskeletal system was not significantly associated with better academic performance.

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.

Lipid profile of cerebrospinal fluid in multiple sclerosis patients: a potential tool for diagnosis.

Multiple sclerosis (MS) is a complex multifactorial neuropathology. Although its etiology remains unclear, it has been demonstrated that the immune system attacks myelin, leading to demyelination and axonal damage. The involvement of lipids as one of the main components of myelin sheaths in MS and other demyelinating diseases has been postulated. However, it is still a matter of debate whether specific alteration patterns exist over the disease course. Here, using a lipidomic approach, we demonstrated that, at the time of diagnosis, the cerebrospinal fluid of MS patients presented differences in 155 lipid species, 47 of which were identified. An initial hierarchical clusterization was used to classify MS patients based on the presence of 25 lipids. When a supervised method was applied in order to refine this classification, a lipidomic signature was obtained. This signature was composed of 15 molecules belonging to five different lipid families including fatty acids (FAs). An FA-targeted approach revealed differences in two members of this family: 18:3n3 and 20:0 (arachidic acid). These results reveal a CSF lipidomic signature in MS patients at the time of diagnosis that might be considered as a potential diagnostic tool.

[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.

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.

[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.

Revisión de la diana para la estimulación cerebral profunda de la cefalea en racimos crónica / Review of the target for the deep brain stimulation of chronic cluster headache

La cefalea en racimos pertenece al grupo de las cefalalgias trigeminales autosómicas. Aunque su fisiopatología no está suficientemente clara, se cree que una disfunción hipotalámica es la causante de este tipo de cefaleas. Desde 001 se ha tratado a más de 50 pacientes con estimulación cerebral en el hipotálamo posterior. Los resultados obtenidos hasta la fecha son de mejoría en más del 60% de los casos y se ha abierto un camino prometedor para el tratamiento de la cefalea en racimos crónica rebelde a tratamiento farmacológico. La diana quirúrgica utilizada hasta ahora se basa en la disfunción del hipotálamo posteroinferior como origen de la cefalea en racimos; sin embargo, hay varias cuestiones no resueltas como son, entre otras, la falta de demostración de que el hipotálamo posteroinferior es el generador de las cefaleas, no existe un consenso sobre la anatomía de la diana quirúrgica y la variabilidad de estructuras anatómicas neuroestimuladas en estos pacientes. El objetivo de este artículo es hacer una revisión crítica de la diana utilizada en esta patología y proponer, sobre la base de conceptos fisiopatológicos, otra diana que explique el efecto beneficioso de la estimulación cerebral profunda en estos pacientes (AU)

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 (AU)

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.