We combined real-time calcium-based neural activity imaging with whole-cell patch-clamp recording techniques to map the spatial organization and analyze electrophysiological properties of respiratory neurons forming the circuit transmitting rhythmic drive from the pre-Bötzinger complex (pre-BötC) through premotoneurons to hypoglossal (XII) motoneurons. Inspiratory pre-BötC neurons, XII premotoneurons (preMNs), and XII motoneurons (MNs) were retrogradely labeled with Ca 2ϩ -sensitive dye in neonatal rat in vitro brainstem slices. PreMN cell bodies were arrayed dorsomedially to pre-BötC neurons with little spatial overlap; axonal projections to MNs were ipsilateral. Inspiratory MNs were distributed in dorsal and ventral subnuclei of XII. Voltage-clamp recordings revealed that two currents, persistent sodium current (NaP) and K ϩ -dominated leak current (Leak), primarily contribute to preMN/MN subthreshold current-voltage relationships. NaP or Leak conductance densities in preMNs and MNs were not significantly different. We quantified preMN and MN action potential time course and spike frequency-current ( f-I) relationships and found no significant differences in repetitive spiking dynamics, steady-state f-I gains, and afterpolarizing potentials. Rhythmic synaptic drive current densities were similar in preMNs and MNs. Our results indicate that, despite topographic and morphological differences, preMNs and MNs have some common intrinsic membrane, synaptic integration, and spiking properties that we postulate ensure fidelity of inspiratory drive transmission and conversion of synaptic drive into (pre)motor output. There also appears to be a common architectonic organization for some respiratory drive transmission circuits whereby many preMNs are spatially segregated from pre-BötC rhythm-generating neurons, which we hypothesize may facilitate downstream integration of convergent inputs for premotor pattern formation.

At present, the field of e-health interventions for the treatment of anxiety or depression in children and adolescents with long-term physical conditions is limited to five low quality trials. The very low-quality of the evidence means the effects of e-health interventions are uncertain at this time, especially in children aged under 10 years.Although it is too early to recommend e-health interventions for this clinical population, given their growing number, and the global improvement in access to technology, there appears to be room for the development and evaluation of acceptable and effective technologically-based treatments to suit children and adolescents with long-term physical conditions.

Microelectrode recordings are a useful adjunctive method for subthalamic nucleus localization during deep brain stimulation surgery for Parkinson's disease. Attempts to quantitate and standardize this process, using single computational measures of neural activity, have been limited by variability in patient neurophysiology and recording conditions. Investigators have suggested that a multi-feature approach may be necessary for automated approaches to perform within acceptable clinical standards. We present a novel data visualization algorithm and several unique features that address these shortcomings. The algorithm extracts multiple computational features from the microelectrode neurophysiology and integrates them with tools from unsupervised machine learning. The resulting colour-coded map of neural activity reveals activity transitions that correspond to the anatomic boundaries of subcortical structures. Using these maps, a non-neurophysiologist is able to achieve sensitivities of 90% and 95% for STN entry and exit, respectively, to within 0.5 mm accuracy of the current gold standard. The accuracy of this technique is attributed to the multi-feature approach. This activity map can simplify and standardize the process of localizing the subthalamic nucleus (STN) for neurostimulation. Because this method does not require a stationary electrode for careful recording of unit activity for spike sorting, the length of the operation may be shortened.

Chronic hepatitis C remains a significant medical and economic burden in Canada, affecting nearly 1% of the population. Since the last consensus conference on the management of chronic hepatitis C, major advances have warranted a review of recommended management approaches for these patients. Specifically, direct-acting antiviral agents with dramatically improved rates of virological clearance compared with standard therapy have been developed, and several single nucleotide polymorphisms associated with an increased probability of spontaneous and treatment-induced viral clearance have been identified. In light of this new evidence, a consensus development conference was held in November 2011; the present document highlights the results of the presentations and discussions surrounding these issues. It reviews the epidemiology of hepatitis C in Canada, preferred diagnostic testing approaches and recommendations for the treatment of chronically infected patients with the newly approved protease inhibitors (boceprevir and telaprevir), including those who have previously failed pegylated interferon and ribavirin therapy. In addition, recommendations are made regarding approaches to reducing the burden of hepatitis C in Canada.

SUMMARYDose-dependent PR interval prolongation has been reported in preclinical studies of lacosamide (LCM), a recently U.S. Food and Drug Administration (FDA)-approved antiepileptic drug (AED). Here we report a case of second-degree atrioventricular block (AV) block caused by the addition of LCM to other AEDs known to prolong the PR interval, resulting in hypotension and bradycardia, with consequent seizure exacerbation. The patient recovered completely after withdrawal of LCM. This case demonstrates the need for caution and interval cardiac testing when adding LCM to other AEDs known to prolong the PR interval. KEY WORDS: Lacosamide, Heart block, Arrhythmia. Case ReportA 45-year-old man with frontal lobe epilepsy, seizurefree for 1 year, developed palpitations, dyspnea, and exercise intolerance 1 week prior to hospitalization for recurrent seizure. En route to the hospital, he was noted to have bradycardia (44 bpm) with hypotension (83/64 mm Hg).His medical history included craniopharyngioma at age 6, treated with right frontal craniotomy, resection, radiation, and ventriculoatrial shunting. His course was complicated by right eye blindness and panhypopituitarism with diabetes insipidus, hypothyroidism, and adrenal insufficiency. At age 21, he developed acute lymphocytic leukemia, treated with chemotherapy. At age 23, he developed frontal lobe epilepsy featuring generalized tonic-clonic seizures beginning with stereotyped right arm extension. There was no personal or family history of cardiac conduction disorders.His medications included desmopressin, hydrocortisone, levothyroxine, somatropin, alfuzosin, risedronate, Carbatrol 100 mg po qAM and 200 mg po qPM, oxcarbazepine 600 mg po qAM, 600 mg po qPM, and 1200 mg po qHS, and LCM 200 mg nightly. His only medication change over the last year was LCM replacing zonisamide (ZNS) for unclear reasons 3 months previously, reaching 200 mg 2 months prior to presentation.Initial laboratory evaluation with blood counts, electrolytes, and hepatic enzymes was unremarkable; carbamazepine (CBZ) level was 3.8 lg/ml. Head computerized tomography showed stable right frontal encephalomalacia. Electrocardiography (ECG) showed second-degree AV block (Mobitz I/Wenckebach) with frequent dropped beats and bradycardia. A transvenous pacemaker was placed. After three further seizures, Carbatrol was increased to 200 mg twice daily, continuous intravenous lorazepam was added, and he was transferred to our institution.At our institution, physical examination revealed prior craniotomy, depressed consciousness, and right afferent pupillary defect. Echocardiography, urinalysis, urine toxicology, and endocrine evaluation [including sodium, thyroxine, and morning cortisol] were unremarkable. Thyroid-stimulating hormone was undetectable, as expected. His antiepileptic drugs (AEDs) were continued except for ZNS replacing LCM. Initial cardiac monitoring showed a markedly prolonged PR interval, frequent Mobitz I AV block, and right bundle branch block. Continuous videoelectroencephalography (EEG) ...

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