Length of the Mitral Isthmus But Not Anatomical Location of Ablation Line Predicts Bidirectional Mitral Isthmus Block in Patients Undergoing Catheter Ablation of Persistent Atrial Fibrillation: A Randomized Controlled Trial.

INTRODUCTION: Mitral isthmus (MI) ablation is an effective option in patients undergoing ablation for persistent atrial fibrillation (AF). Achieving bidirectional conduction block across the MI is challenging, and predictors of MI ablation success remain incompletely understood. We sought to determine the impact of anatomical location of the ablation line on the efficacy of MI ablation. METHODS AND RESULTS: A total of 40 consecutive patients (87% male; 54 ± 10 years) undergoing stepwise AF ablation were included. MI ablation was performed in sinus rhythm. MI ablation was performed from the left inferior PV to either the posterior (group 1) or the anterolateral (group 2) mitral annulus depending on randomization. The length of the MI line (measured with the 3D mapping system) and the amplitude of the EGMs at 3 positions on the MI were measured in each patient. MI block was achieved in 14/19 (74%) patients in group 1 and 15/21 (71%) patients in group 2 (P = NS). Total MI radiofrequency time (18 ± 7 min vs. 17 ± 8 min; P = NS) was similar between groups. Patients with incomplete MI block had a longer MI length (34 ± 6 mm vs. 24 ± 5 mm; P < 0.001), a higher bipolar voltage along the MI (1.75 ± 0.74 mV vs. 1.05 ± 0.69 mV; P < 0.01), and a longer history of continuous AF (19 ± 17 months vs. 10 ± 10 months; P < 0.05). In multivariate analysis, decreased length of the MI was an independent predictor of successful MI block (OR 1.5; 95% CI 1.1-2.1; P < 0.05). CONCLUSIONS: Increased length but not anatomical location of the MI predicts failure to achieve bidirectional MI block during ablation of persistent AF.

Persistence of tracer in the application site -a potential confounding factor in nerve regeneration studies

Selective reinnervation of peripheral targets after nerve injury might be assessed by injecting a first tracer in a target before nerve injury to label the original neuronal population, and applying a second tracer after the regeneration period to label the regenerated population. However, altered uptake of tracer, fading, and cell death may interfere with the results. Furthermore, if the first tracer injected remains in the target tissue, available for 're-uptake' by misdirected regenerating axons, which originally innervated another region, then the identification of the original population would be confused. With the aim of studying this problem, the sciatic nerve of adult rats was sectioned and sutured. After 3 days, to allow the distal axon to degenerate avoiding immediate retrograde transport, one of the dyes: Fast Blue (FB), Fluoro-Gold (FG) or Diamidino Yellow (DY), was injected into the tibial branch of the sciatic nerve, or in the skin of one of the denervated digits. Rats survived 2-3 months. The results showed labelled dorsal root ganglion (DRG) cells and motoneurones, indicating that late re-uptake of a first tracer occurs. This phenomenon must be considered when the model of sequential labelling is used for studying the accuracy of peripheral reinnervation.

Collagen (NeuraGen®) nerve conduits and stem cells for peripheral nerve gap repair

Le système nerveux périphérique est responsable de la transmission des impulses motrices, ainsi que de la réception des afférences sensorielles. Les lésions traumatiques des nerfs périphériques conduisent à une impotence fonctionnelle qui peut être dévastant, notamment chez les travailleurs manuels,. La récupération fonctionnelle est donc le but principal dans chirurgie des nerfs périphériques. Malheureusement, une suture directe des moignons nerveux est souvent impossible dans le contexte des traumatismes complexes qui surviennent lors des accidents. La suture nerveuse par interposition d'autogreffe reste le gold standard dans la pratique chirurgicale mais nécessite le sacrifice d'un nerf donneur, avec dysesthésie et possibles douleurs neuropathiques conséquentes. Alternativement, des guides tubulaires pour les nerfs peuvent être utilisées si le gap nerveux est inférieur à 3 cm. Plusieurs guides résorbables en collagène sont approuve en Europe et aux Etas Unis (FDA). Dans cette étude, des conduits de collagène ont été associe a des cellules régénératives (cellules souches adultes) comme stratégie supplémentaire de régénération. Une fois testé le rapport des cellules avec le biomatériau (NeuraGen® nerve guides) in vitro, une étude in vivo dans le rat a été effectuée. Les différents groupes de conduits ont été supplémentés respectivement avec Schwann cells (SC); avec cellules souches adultes dérivées de la moelle épinière, différentiées en cellules "Schwann-like" (dMSC); avec cellules souches adultes dérivées de la graisse, différentiées en cellules "Schwann-like" (dASC). Un groupe de conduits avec du milieu de culture sans cellules a été utilisé comme group control. Les conduits ont été utilisés pour combler un gap de 1cm dans un model de section totale du nerf sciatique chez le rat. Deux semaines post implantation, une analyse immuno-histochimique a été effectuée pour évaluer la régénération axonales et l'infiltration de cellules de Schwann au niveau du conduit. Les cellules ont montré une adhérence efficace aux parois de collagène. En particulier, les cellules de Schwann ont montré une amélioration significative au niveau du sprouting distale. Par contre, aucune différence significative n'a été remarquée entre les groupes pour le sprouting axonale proximal. De plus, si les cellules souches ont montré un pattern de sprouting diffus, les cellules de Schwann ont par contre garanti un cône de croissance typique, associé a une affinité remarquable pour les parois de collagène. NeuraGen® guides pourraient donc être un moyen adapté a l'association avec la thérapie cellulaire en raison de la bonne adhérence des cellules au biomatériau. Des modifications de surface dans le but d'améliorer la performance neurotrophique cellulaire in vivo (e.g. peptides de matrice extracellulaire) pourront être utilisées dans des applications futures.

Estimations of topographically correct regeneration to nerve branches and skin after peripheral nerve injury and repair.

Peripheral nerve injury is typically associated with long-term disturbances in sensory localization, despite nerve repair and regeneration. Here, we investigate the extent of correct reinnervation by back-labeling neuronal soma with fluorescent tracers applied in the target area before and after sciatic nerve injury and repair in the rat. The subpopulations of sensory or motor neurons that had regenerated their axons to either the tibial branch or the skin of the third hindlimb digit were calculated from the number of cell bodies labeled by the first and/or second tracer. Compared to the normal control side, 81% of the sensory and 66% of the motor tibial nerve cells regenerated their axons back to this nerve, while 22% of the afferent cells from the third digit reinnervated this digit. Corresponding percentages based on quantification of the surviving population on the experimental side showed 91%, 87%, and 56%, respectively. The results show that nerve injury followed by nerve repair by epineurial suture results in a high but variable amount of topographically correct regeneration, and that proportionally more neurons regenerate into the correct proximal nerve branch than into the correct innervation territory in the skin

Myelin-associated proteins block the migration of olfactory ensheathing cells: an in vitro study using single cell tracking and traction force microscopy

Newly generated olfactory receptor axons grow from the peripheral to the central nervous system aided by olfactory ensheathing cells (OECs). Thus, OEC transplantation has emerged as a promising therapy for spinal cord injuries and for other neural diseases. However, these cells do not present a uniform population, but, instead, a functionally heterogeneous population that exhibits a variety of responses including adhesion, repulsion and crossover during cell-cell and cell-matrix interactions. Some studies report that the migratory properties of OECs are compromised by inhibitory molecules and potentiated by chemical gradients. Here, we demonstrated that rodent OECs express all the components of the Nogo Receptor complex and that their migration is blocked by Myelin. Next, we used cell tracking and traction force microscopy to analyze OEC migration and its mechanical properties over Myelin. Our data relate the absence of traction force of OEC with lower migratory capacity, which correlates with changes in the F-Actin cytoskeleton and focal adhesion distribution. Lastly, OEC traction force and migratory capacity is enhanced after cell incubation with the Nogo Receptor inhibitor NEP1-40.

Comparison of acute non-visual bright light responses in patients with optic nerve disease, glaucoma and healthy controls.

This study examined the effect of optic nerve disease, hence retinal ganglion cell loss, on non-visual functions related to melanopsin signalling. Test subjects were patients with bilateral visual loss and optic atrophy from either hereditary optic neuropathy (n = 11) or glaucoma (n = 11). We measured melatonin suppression, subjective sleepiness and cognitive functions in response to bright light exposure in the evening. We also quantified the post-illumination pupil response to a blue light stimulus. All results were compared to age-matched controls (n = 22). Both groups of patients showed similar melatonin suppression when compared to their controls. Greater melatonin suppression was intra-individually correlated to larger post-illumination pupil response in patients and controls. Only the glaucoma patients demonstrated a relative attenuation of their pupil response. In addition, they were sleepier with slower reaction times during nocturnal light exposure. In conclusion, glaucomatous, but not hereditary, optic neuropathy is associated with reduced acute light effects. At mild to moderate stages of disease, this is detected only in the pupil function and not in responses conveyed via the retinohypothalamic tract such as melatonin suppression.

Redundant nerve roots of the cauda equina: review of the literature

In imaging diagnosis, redundant nerve roots of the cauda equina are characterized by the presence of elongated, enlarged and tortuous nerve roots in close relationship with a high-grade lumbar spinal canal stenosis. This is not an independent entity, but it is believed to be a consequence of the chronic compression at the level of the lumbar canal stenosis and thus may be part of the natural history of lumbar spinal stenosis. The present paper is aimed at reviewing the histopathological, electrophysiological and imaging findings, particularly at magnetic resonance imaging, as well as the clinical meaning of this entity. As the current assessment of canal stenosis and root compression is preferably performed by means of magnetic resonance imaging, this is the imaging method by which the condition is identified. The recognition of redundant nerve roots at magnetic resonance imaging is important, particularly to avoid misdiagnosing other conditions such as intradural arteriovenous malformations. The literature approaching the clinical relevance of the presence of redundant nerve roots is controversial. There are articles suggesting that the pathological changes of the nerve roots are irreversible at the moment of diagnosis and therefore neurological symptoms are less likely to improve with surgical decompression, but such concept is not a consensus.

Antibody levels against GLURP R2, MSP1 block 2 hybrid and AS202.11 and the risk of malaria in children living in hyperendemic (Burkina Faso) and hypo-endemic (Ghana) areas.

Differences in parasite transmission intensity influence the process of acquisition of host immunity to Plasmodium falciparum malaria and ultimately, the rate of malaria related morbidity and mortality. Potential vaccines being designed to complement current intervention efforts therefore need to be evaluated against different malaria endemicity backgrounds. The associations between antibody responses to the chimeric merozoite surface protein 1 block 2 hybrid (MSP1 hybrid), glutamate-rich protein region 2 (GLURP R2) and the peptide AS202.11, and the risk of malaria were assessed in children living in malaria hyperendemic (Burkina Faso, n = 354) and hypo-endemic (Ghana, n = 209) areas. Using the same reagent lots and standardized protocols for both study sites, immunoglobulin (Ig) M, IgG and IgG sub-class levels to each antigen were measured by ELISA in plasma from the children (aged 6-72 months). Associations between antibody levels and risk of malaria were assessed using Cox regression models adjusting for covariates. There was a significant association between GLURP R2 IgG3 and reduced risk of malaria after adjusting age of children in both the Burkinabe (hazard ratio 0.82; 95 % CI 0.74-0.91, p < 0.0001) and the Ghanaian (HR 0.48; 95 % CI 0.25-0.91, p = 0.02) cohorts. MSP1 hybrid IgM was associated (HR 0.85; 95 % CI 0.73-0.98, p = 0.02) with reduced risk of malaria in Burkina Faso cohort while IgG against AS202.11 in the Ghanaian children was associated with increased risk of malaria (HR 1.29; 95 % CI 1.01-1.65, p = 0.04). These findings support further development of GLURP R2 and MSP1 block 2 hybrid, perhaps as a fusion vaccine antigen targeting malaria blood stage that can be deployed in areas of varying transmission intensity.

Extrafascial injection for interscalene brachial plexus block reduces respiratory complications compared with a conventional intrafascial injection: a randomized, controlled, double-blind trial?.

BACKGROUND: Hemidiaphragmatic paresis after ultrasound-guided interscalene brachial plexus block is reported to occur in up to 100% of patients. We tested the hypothesis that an injection lateral to the brachial plexus sheath reduces the incidence of hemidiaphragmatic paresis compared with a conventional intrafascial injection, while providing similar analgesia. METHODS: Forty ASA I-III patients undergoing elective shoulder and clavicle surgery under general anaesthesia were randomized to receive an ultrasound-guided interscalene brachial plexus block for analgesia, using 20 ml bupivacaine 0.5% with epinephrine 1:200 000 injected either between C5 and C6 within the interscalene groove (conventional intrafascial injection), or 4 mm lateral to the brachial plexus sheath (extrafascial injection). The primary outcome was incidence of hemidiaphragmatic paresis (diaphragmatic excursion reduction >75%), measured by M-mode ultrasonography, before and 30 min after the procedure. Secondary outcomes were forced vital capacity, forced expiratory volume in 1 s, and peak expiratory flow. Additional outcomes included time to first opioid request and pain scores at 24 h postoperatively (numeric rating scale, 0-10). RESULTS: The incidences of hemidiaphragmatic paresis were 90% (95% CI: 68-99%) and 21% (95% CI: 6-46%) in the conventional and extrafascial injection groups, respectively (P<0.0001). Other respiratory outcomes were significantly better preserved in the extrafascial injection group. The mean time to first opioid request was similar between groups (conventional: 802 min [95% CI: 620-984 min]; extrafascial: 973 min [95% CI: 791-1155 min]; P=0.19) as were pain scores at 24 h postoperatively (conventional: 1.6 [95% CI: 0.9-2.2]; extrafascial: 1.6 [95% CI: 0.8-2.4]; P=0.97). CONCLUSIONS: Ultrasound-guided interscalene brachial plexus block with an extrafascial injection reduces the incidence of hemidiaphragmatic paresis and impact on respiratory function while providing similar analgesia, when compared with a conventional injection. CLINICAL TRIAL REGISTRATION: NCT02074397.

Celiac plexus block: an anatomical study and simulation using computed tomography

Objective: To analyze anatomical variations associated with celiac plexus complex by means of computed tomography simulation, assessing the risk for organ injury as the transcrural technique is utilized. Materials and Methods: One hundred eight transaxial computed tomography images of abdomen were analyzed. The aortic-vertebral, celiac trunk (CeT)-vertebral, CeT-aortic and celiac-aortic-vertebral topographical relationships were recorded. Two needle insertion pathways were drawn on each of the images, at right and left, 9 cm and 4.5 cm away from the midline. Transfixed vital organs and gender-related associations were recorded. Results: Aortic-vertebral - 45.37% at left and 54.62% in the middle; CeT-vertebral - T12, 36.11%; T12-L1, 32.4%; L1, 27.77%; T11-T12, 2.77%; CeT-aortic - 53.7% at left and 46.3% in the middle; celiac-aortic-vertebral - L-l, 22.22%; M-m, 23.15%; L-m, 31.48%; M-l, 23.15%. Neither correspondence on the right side nor significant gender-related associations were observed. Conclusion: Considering the wide range of abdominal anatomical variations and the characteristics of needle insertion pathways, celiac plexus block should not be standardized. Imaging should be performed prior to the procedure in order to reduce the risks for injuries or for negative outcomes to patients. Gender-related anatomical variations involved in celiac plexus block should be more deeply investigated, since few studies have addressed the subject.

Compressive neuropathy of the first branch of the lateral plantar nerve: a study by magnetic resonance imaging

Abstract Objective: To assess the prevalence of isolated findings of abnormalities leading to entrapment of the lateral plantar nerve and respective branches in patients complaining of chronic heel pain, whose magnetic resonance imaging exams have showed complete selective fatty atrophy of the abductor digiti quinti muscle. Materials and Methods: Retrospective, analytical, and cross-sectional study. The authors selected magnetic resonance imaging of hindfoot of 90 patients with grade IV abductor digiti quinti muscle atrophy according to Goutallier and Bernageau classification. Patients presenting with minor degrees of fatty muscle degeneration (below grade IV) and those who had been operated on for nerve decompression were excluded. Results: A female prevalence (78.8%) was observed, and a strong correlation was found between fatty muscle atrophy and plantar fasciitis in 21.2%, and ankle varices, in 16.8% of the patients. Conclusion: Fatty atrophy of the abductor digiti quinti muscle is strongly associated with neuropathic alterations of the first branch of the lateral plantar nerve. The present study showed a significant association between plantar fasciitis and ankle varices with grade IV atrophy of the abductor digiti quinti muscle.

Spinal Cord T-Cell Infiltration in the Rat Spared Nerve Injury Model: A Time Course Study.

The immune system is involved in the development of neuropathic pain. In particular, the infiltration of T-lymphocytes into the spinal cord following peripheral nerve injury has been described as a contributor to sensory hypersensitivity. We used the spared nerve injury (SNI) model of neuropathic pain in Sprague Dawley adult male rats to assess proliferation, and/or protein/gene expression levels for microglia (Iba1), T-lymphocytes (CD2) and cytotoxic T-lymphocytes (CD8). In the dorsal horn ipsilateral to SNI, Iba1 and BrdU stainings revealed microglial reactivity and proliferation, respectively, with different durations. Iba1 expression peaked at D4 and D7 at the mRNA and protein level, respectively, and was long-lasting. Proliferation occurred almost exclusively in Iba1 positive cells and peaked at D2. Gene expression observation by RT-qPCR array suggested that T-lymphocytes attracting chemokines were upregulated after SNI in rat spinal cord but only a few CD2/CD8 positive cells were found. A pronounced infiltration of CD2/CD8 positive T-cells was seen in the spinal cord injury (SCI) model used as a positive control for lymphocyte infiltration. Under these experimental conditions, we show early and long-lasting microglia reactivity in the spinal cord after SNI, but no lymphocyte infiltration was found.