Vagus nerve stimulation for medically refractory epilepsy: efficacy and cost-benefit analysis

Introduction. Vagus nerve stimulation is a novel treatment for patients with medically refractory epilepsy, who are not candidates for conventional epilepsy surgery, or who have had such surgery without optimal outcome. To date only studies with relatively short follow-up are available. In these studies efficacy increased with time and reached a maximum after a period of 6 to 12 months. Implantation of a vagus nerve stimulator requires an important financial investment but a cost-benefit analysis has not been published. Patients and Methods. Our own experience with VNS in Gent comprises 15 patients with mean age of 29 years (range: 17-44 years) and mean duration of epilepsy of 18 years (range: 4-32 years). All patients underwent a comprehensive presurgical evaluation and were found not to be suitable candidates for resective epilepsy surgery. Mean post-implantation follow-up is 24 months (range: 7-43 months). In patients with follow-up of at least one year, efficacy of treatment in terms of seizure control and seizure severity was assessed one year before and after the implantation of a vagus nerve stimulator. Epilepsy-related direct medical costs (ERDMC) before and after the implantation were also compared. Results. A mean reduction of seizure frequency from 14 seizures/month (range: 2-40/month) to 8 seizures/month (range: 0-30/month) was achieved (Wilcoxon signed rank test n = 14; p = 0.0016). Five patients showed a marked seizure reduction of greater than or equal to 50%; 6 became free of complex partial seizures, 3 of whom became entirely seizure free for more than 12 months; 2 patients had a worthwhile reduction of seizure frequency between 30-50%; in 2 patients seizure frequency reduction has remained practically unchanged. Seizure freedom or greater than or equal to 50% seizure reduction was achieved within the first 4 months after implantation in 6/11 patients. Before the implantation, the mean yearly epilepsy-related direct medical costs per patient were estimated to be 8830 US$(n = 13; range: 1879-31129 US$; sd = 7667); the average number of hospital admission days per year was 21 (range: 4-100; sd = 25.7). In the 12 months after implantation, ERDMC had decreased to 4215 US$(range: 615-11794 US$; sd = 3558) (Wilcoxon signed rank test n = 13; p = 0.018) and the average number of admission days to 8 (range: 0-35) (Wilcoxon signed rank test n = 13; p = 0.023). Conclusion. VNS is an effective treatment of refractory epilepsy and remains effective during long-term follow-up. Cost-benefit analysis suggests that the cost of VNS is saved within two years following implantation

Adatom Fe(III) on the hematite surface: Observation of a key reactive surface species

The reactivity of a mineral surface is determined by the variety and population of different types of surface sites (e.g., step, kink, adatom, and defect sites). The concept of "adsorbed nutrient" has been built into crystal growth theories, and many other studies of mineral surface reactivity appeal to ill-defined "active sites." Despite their theoretical importance, there has been little direct experimental or analytical investigation of the structure and properties of such species. Here, we use ex-situ and in-situ scanning tunneling microcopy (STM) combined with calculated images based on a resonant tunneling model to show that observed nonperiodic protrusions and depressions on the hematite (001) surface can be explained as Fe in an adsorbed or adatom state occupying sites different from those that result from simple termination of the bulk mineral. The number of such sites varies with sample preparation history, consistent with their removal from the surface in low pH solutions

International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020)

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice

Polymorphism: an evaluation of the potential risk to the quality of drug products from the Farmácia Popular Rede Própria

Polymorphism in solids is a common phenomenon in drugs, which can lead to compromised quality due to changes in their physicochemical properties, particularly solubility, and, therefore, reduce bioavailability. Herein, a bibliographic survey was performed based on key issues and studies related to polymorphism in active pharmaceutical ingredient (APIs) present in medications from the Farmácia Popular Rede Própria. Polymorphism must be controlled to prevent possible ineffective therapy and/or improper dosage. Few mandatory tests for the identification and control of polymorphism in medications are currently available, which can result in serious public health concerns

Tubular aggregates in autoimmune Lambert-Eaton myasthenic syndrome

Tubular aggregates are accumulations of densely packed tubules in muscle fibers, occurring in distinct hereditary and acquired disorders. We present a patient with tubular aggregates and autoimmune Lambert-Eaton myasthenic syndrome. Initially, he showed mild proximal weakness, borderline decrement on 3 Hz stimulation, and slightly elevated creatine kinase. Muscle biopsy revealed tubular aggregates in type II fibers. Due to a good response to pyridostigmine, a limb-girdle myasthenia with tubular aggregates was suspected, but genetic analyses of GFPT1, DPGAT1, and ALG2 were normal. Two years later, the patient presented with progressive weakness and autonomic dysfunction. 17% decrement on 3 Hz stimulation and 100% increment after brief exercise were revealed. Autoantibodies to voltage-gated calcium-channels confirmed the diagnosis of Lambert-Eaton myasthenic syndrome. Steroids, azathioprine, and 3,4-diaminopyridine significantly improved symptoms. No tumor was found during follow-up. This is the first report about tubular aggregates associated with an acquired myasthenic syndrome. Our findings are important because of the therapeutic implications.status: publishe

Towards a functional pathology of hereditary neuropathies

A growing number of hereditary neuropathies have been assigned to causative gene defects in recent years. The study of human nerve biopsy samples has contributed substantially to the discovery of many of these neuropathy genes. Genotype-phenotype correlations based on peripheral nerve pathology have provided a comprehensive picture of the consequences of these mutations. Intriguingly, several gene defects lead to distinguishable lesion patterns that can be studied in nerve biopsies. These characteristic features include the loss of certain nerve fiber populations and a large spectrum of distinct structural changes of axons, Schwann cells and other components of peripheral nerves. In several instances the lesion patterns are directly or indirectly linked to the known functions of the mutated gene. The present review is designed to provide an overview on these characteristic patterns. It also considers other aspects important for the manifestation and pathology of hereditary neuropathies including the role of inflammation, effects of chemotherapeutic agents and alterations detectable in skin biopsies.status: publishe

Increased hippocampal extracellular noradrenalin concentration contributes to the anticonvulsant effect of VNS in the focal pilocarpine rat model for limbic seizures

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Elevation of plasma 1-deoxy-sphingolipids in type 2 diabetes mellitus: a susceptibility to neuropathy?

Diabetic distal sensorimotor polyneuropathy (DSPN) is a frequent, disabling complication of diabetes mellitus. There is increasing evidence that sphingolipids play a role in insulin resistance and type 2 diabetes (T2DM). Whether neurotoxic 1-deoxy-sphingolipids are elevated in DSPN patients' plasma and whether levels correlate to the DSPN stage were examined.status: publishe