Neurophysiological investigations of drug resistant epilepsy patients treated with vagus nerve stimulation to differentiate responders from non-responders

Background and purpose In patients treated with vagus nerve stimulation (VNS) for drug resistant epilepsy (DRE), up to a third of patients will eventually not respond to the therapy. As VNS therapy requires surgery for device implantation, prediction of response prior to surgery is desirable. It is hypothesized that neurophysiological investigations related to the mechanisms of action of VNS may help to differentiate VNS responders from non-responders prior to the initiation of therapy. Methods In a prospective series of DRE patients, polysomnography, heart rate variability (HRV) and cognitive event related potentials were recorded. Polysomnography and HRV were repeated after 1 year of treatment with VNS. Polysomnography, HRV and cognitive event related potentials were compared between VNS responders (>= 50% reduction in seizure frequency) and non-responders. Results Fifteen out of 30 patients became VNS responders after 1 year of VNS treatment. Prior to treatment with VNS, the amount of deep sleep (NREM 3), the HRV high frequency (HF) power and the P3b amplitude were significantly different in responders compared to non-responders (P = 0.007; P = 0.001; P = 0.03). Conclusion Three neurophysiological parameters, NREM 3, HRV HF and P3b amplitude, were found to be significantly different in DRE patients who became responders to VNS treatment prior to initiation of their treatment with VNS. These non-invasive recordings may be used as characteristics for response in future studies and help avoid unsuccessful implantations. Mechanistically these findings may be related to changes in brain regions involved in the so-called vagal afferent network

Does enternal nutrition affect clinical outcome? A systematic review of the randomized trials

Background: Both parenteral nutrition (PN) and enteral nutrition (EN) are widely advocated as adjunctive care in patients with various diseases. A systematic review of 82 randomized controlled trials (RCTs) of PN published in 2001 found little, if any, effect on mortality, morbidity, or duration of hospital stay; in some situations, PN increased infectious complication rates. Objective: To assess the effect of EN or volitional nutrition support (VNS) in individual disease states from available randomized controlled trials (RCTs). Design: We conducted a systematic review. RCTs comparing EN or VNS to untreated controls, or comparing EN to PN, were identified and separated according to the underlying disease state. Meta-analysis was performed when at least 3 RCTs provided data. The evidence from the RCTs was summarized into one of five grades. A or B indicated the presence of strong or weak (low quality RCTs) evidence supporting the use of the intervention. C indicated a lack of adequate evidence to make any decision about efficacy. D indicated that limited data could not support the intervention. E indicated either that strong data found no effect, or that either strong or weak data suggested that the intervention caused harm. Patients and settings: RCTs could include either hospitalized or non-hospitalized patients. The EN or VNS had to be provided as part of a treatment plan for an underlying disease process. Interventions: The RCT had to compare recipients of either EN or VNS to controls not receiving any type of artificial nutrition or had to compare recipients of EN with recipients of PN. Outcome measures: Mortality, morbidity (disease-specific), duration of hospitalization, cost, or interventional complications. Summary of grading: A – No indication was identified. B – EN or VNS in the perioperative patient or in patients with chronic liver disease; EN in critically ill patients or low birth weight infants (trophic feeding); VNS in malnourished geriatric patients. (The low quality trials found a significant difference in survival favoring the VNS recipients in the malnourished geriatric patient trials; two high quality trials found non-significant differences that favored VNS as well.) C – EN or VNS in liver transplantation, cystic fibrosis, renal failure, pediatric conditions other than low birth weight infants, well-nourished geriatric patients, non-stroke neurologic conditions, AIDS; EN in acute pancreatitis, chronic obstructive pulmonary disease, non-malnourished geriatric patients; VNS in inflammatory bowel disease, arthritis, cardiac disease, pregnancy, allergic patients, preoperative bowel preparation D – EN or VNS in patients receiving non-surgical cancer treatment or in patients with hip fractures; EN in patients with inflammatory bowel disease; VNS in patients with chronic obstructive pulmonary disease E – EN in the first week in dysphagic, or VNS at any time in non-dysphagic, stroke patients who are not malnourished; dysphagia persisting for weeks will presumably ultimately require EN. Conclusions: There is strong evidence for not using EN in the first week in dysphagic, and not using VNS at all in non-dysphagic, stroke patients who are not malnourished. There is reasonable evidence for using VNS in malnourished geriatric patients. The recommendations to consider EN/VNS in perioperative/liver/critically ill/low birth weight patients are limited by the low quality of the RCTs. No evidence could be identified to justify the use of EN/VNS in other disease states

Efficacy of needle-placement technique in radiofrequency ablation for treatment of lumbar facet arthropathy.

BACKGROUND:Many studies have assessed the efficacy of radiofrequency ablation to denervate the facet joint as an interventional means of treating axial low-back pain. In these studies, varying procedural techniques were utilized to ablate the nerves that innervate the facet joints. To date, no comparison studies have been performed to suggest superiority of one technique or even compare the prevalence of side effects and complications. MATERIALS AND METHODS:A retrospective chart review was performed on patients who underwent a lumbar facet denervation procedure. Each patient's chart was analyzed for treatment technique (early versus advanced Australian), preprocedural visual numeric scale (VNS) score, postprocedural VNS score, duration of pain relief, and complications. RESULTS:Pre- and postprocedural VNS scores and change in VNS score between the two groups showed no significant differences. Patient-reported benefit and duration of relief was greater in the advanced Australian technique group (P=0.012 and 0.022, respectively). The advanced Australian technique group demonstrated a significantly greater median duration of relief (4 months versus 1.5 months, P=0.022). Male sex and no pain-medication use at baseline were associated with decreased postablation VNS scores, while increasing age and higher preablation VNS scores were associated with increased postablation VNS scores. Despite increasing age being associated with increased postablation VNS scores, age and the advanced Australian technique were found to confer greater patient self-reported treatment benefit. CONCLUSION:The advanced Australian technique provides a significant benefit over the early Australian technique for the treatment of lumbar facet pain, both in magnitude and duration of pain relief

Vagus nerve stimulation paired with tactile training improved sensory function in a chronic stroke patient

Background: Recent studies indicate that vagus nerve stimulation (VNS) paired with rehabilitation can enhance neural plasticity in the primary sensory and motor cortices, improve forelimb function after stroke in animal models and improve motor function in patients with arm weakness after stroke. OBJECTIVE:To gain “first-in-man” experience of VNS paired with tactile training in a patient with severe sensory impairment after stroke. Methods: During the long-term follow-up phase of a clinical trial of VNS paired with motor rehabilitation, a 71-year-old man who had made good motor recovery had ongoing severe sensory loss in his left hand and arm. He received VNS paired with tactile therapy in an attempt to improve his sensory function. During twenty 2-hour sessions, each passive and active tactile event was paired with a 0.5 second burst of 0.8 mA VNS. Sensory function was measured before, halfway through, and after this therapy. Results: The patient did not report any side effects during or following VNS+Tactile therapy. Quantitative measures revealed lasting and clinically meaningful improvements in tactile threshold, proprioception, and stereognosis. After VNS+Tactile therapy, the patient was able to detect tactile stimulation to his affected hand that was eight times less intense, identify the joint position of his fingers in the affected hand three times more often, and identify everyday objects using his affected hand seven times more often, compared to baseline. Conclusions: Sensory function significantly improved in this man following VNS paired with tactile stimulation. This approach merits further study in controlled clinical trials

The continuous p-centre problem: An investigation into variable neighbourhood search with memory

A VNS-based heuristic using both a facility as well as a customer type neighbourhood structure is proposed to solve the p-centre problem in the continuous space. Simple but effective enhancements to the original Elzinga-Hearn algorithm as well as a powerful ‘locate-allocate’ local search used within VNS are proposed. In addition, efficient implementations in both neighbourhood structures are presented. A learning scheme is also embedded into the search to produce a new variant of VNS that uses memory. The effect of incorporating strong intensification within the local search via a VND type structure is also explored with interesting results. Empirical results, based on several existing data set (TSP-Lib) with various values of p, show that the proposed VNS implementations outperform both a multi-start heuristic and the discrete-based optimal approach that use the same local search

Vagus Nerve Stimulation in Refractory Epilepsy: Effects on Pro- and Anti-Inflammatory Cytokines in Peripheral Blood

Objective: The vagus nerve has important immunological functions that may be relevant for its anticonvulsive action. We postulate that this anticonvulsive action is activated by a shift in the immune system resulting in a reduction of neurotoxic and an increase of neuroprotective tryptophan metabolites. Methods: Eleven patients with refractory epilepsy and 11 controls matched for age and gender were included in this study. The primary outcome measure was a 50% seizure reduction. Other variables were pro-inflammatory cytokines IL-6 and TNF-alpha, anti-inflammatory cytokine IL-10, cortisol, and the tryptophan metabolites 3-hydroxykynurenine (3-OH-KYN), kynurenic acid (KYNA), kynurenine, serotonin (5-HT) and 5-hydroxyindol acetic acid (5-HIAA). Blood samples were scheduled during baseline, and in week 28 of add-on treatment. Results: IL-6 levels were higher in the responders than in the control group, and decreased after vagus nerve stimulation (VNS), whereas IL-10 was low and increased after VNS. In nonresponders, VNS resulted in an increase of IL-6 plasma levels and in a decrease of IL-10. Cortisol concentrations are higher in the epilepsy group than in the control group. After VNS, these concentrations decreased. The concentrations of the tryptophan metabolites were lower in the epilepsy group than in the control group. The KYNA ratios are defined as the ratio of neuroprotective KYNA versus neurotoxic 3-OH-KYN and KYNA versus neurotoxic kynurenine: these ratios were lower in epilepsy patients than in controls, and they both moderately increased after VNS. Conclusion: The outcome of this preliminary study indicates that VNS causes a rebalancing of the immune system. This results in: (1) a reduction of neurotoxic and an increase of neuroprotective kynurenine metabolites and (2) in the normalization of cortisol levels. Copyright (C) 2010 S. Karger AG, Base

Solving the minimum labelling spanning tree problem using hybrid local search

Given a connected, undirected graph whose edges are labelled (or coloured), the minimum labelling spanning tree (MLST) problem seeks a spanning tree whose edges have the smallest number of distinct labels (or colours). In recent work, the MLST problem has been shown to be NP-hard and some effective heuristics (Modified Genetic Algorithm (MGA) and Pilot Method (PILOT)) have been proposed and analyzed. A hybrid local search method, that we call Group-Swap Variable Neighbourhood Search (GS-VNS), is proposed in this paper. It is obtained by combining two classic metaheuristics: Variable Neighbourhood Search (VNS) and Simulated Annealing (SA). Computational experiments show that GS-VNS outperforms MGA and PILOT. Furthermore, a comparison with the results provided by an exact approach shows that we may quickly obtain optimal or near-optimal solutions with the proposed heuristic