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.

Technical aspects of neurostimulation: Focus on equipment, electric field modeling, and stimulation protocols.

Neuromodulation is a field of science, medicine, and bioengineering that encompasses implantable and non-implantable technologies for the purpose of improving quality of life and functioning of humans. Brain neuromodulation involves different neurostimulation techniques: transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), vagus nerve stimulation (VNS), and deep brain stimulation (DBS), which are being used both to study their effects on cognitive brain functions and to treat neuropsychiatric disorders. The mechanisms of action of neurostimulation remain incompletely understood. Insight into the technical basis of neurostimulation might be a first step towards a more profound understanding of these mechanisms, which might lead to improved clinical outcome and therapeutic potential. This review provides an overview of the technical basis of neurostimulation focusing on the equipment, the present understanding of induced electric fields, and the stimulation protocols. The review is written from a technical perspective aimed at supporting the use of neurostimulation in clinical practice.

Therapeutic drug monitoring-based dose optimisation of piperacillin and meropenem: a randomised controlled trial.

PURPOSE: There is variability in the pharmacokinetics (PK) of antibiotics (AB) in critically ill patients. Therapeutic drug monitoring (TDM) could overcome this variability and increase PK target attainment. The objective of this study was to analyse the effect of a dose-adaption strategy based on daily TDM on target attainment. METHODS: This was a prospective, partially blinded, and randomised controlled trial in patients with normal kidney function treated with meropenem (MEM) or piperacillin/tazobactam (PTZ). The intervention group underwent daily TDM, with dose adjustment when necessary. The predefined PK/pharmacodynamic (PK/PD) target was 100% fT>4MIC [percentage of time during a dosing interval that the free (f) drug concentration exceeded 4 times the MIC]. The control group received conventional treatment. The primary endpoint was the proportion of patients that reached 100% fT>4MIC and 100 % fT>MIC at 72 h. RESULTS: Forty-one patients (median age 56 years) were included in the study. Pneumonia was the primary infectious diagnosis. At baseline, 100% fT>4MIC was achieved in 21% of the PTZ patients and in none of the MEM patients; 100% fT>MIC was achieved in 71% of the PTZ patients and 46 % of the MEM patients. Of the patients in the intervention group, 76 % needed dose adaptation, and five required an additional increase. At 72 h, target attainment rates for 100% fT>4MIC and 100% fT>MIC were higher in the intervention group: 58 vs. 16%, p = 0.007 and 95 vs. 68%, p = 0.045, respectively. CONCLUSIONS: Among critically ill patients with normal kidney function, a strategy of dose adaptation based on daily TDM led to an increase in PK/PD target attainment compared to conventional dosing.

[Report of a case of Acanthamoeba keratitis]. / A propos d'un cas de kératite à Acanthamoeba.

CLINICAL REPORT: A clinical report of a contact lenses wearer with Acanthamoeba keratitis pointed out the diagnosis problem. The medical treatment is needed previously to any surgery. Finally the patient underwent enucleation. DISCUSSION: The authors are considering the microbiological aspects and laboratory techniques are described. CONCLUSION: For this very severe but hopefully rare pathology, the sooner the treatment the best. A therapeutic approach is described.