Neurofeedback and epilepsy: Renaissance of an old self-regulation method?

Neurofeedback is a brain-computer interface tool enabling the user to self-regulate their neuronal activity, and ultimately, induce long-term brain plasticity, making it an interesting instrument to cure brain disorders. Although this method has been used successfully in the past as an adjunctive therapy in drug-resistant epilepsy, this approach remains under-explored and deserves more rigorous scientific inquiry. In this review, we present early neurofeedback protocols employed in epilepsy and provide a critical overview of the main clinical studies. We also describe the potential neurophysiological mechanisms through which neurofeedback may produce its therapeutic effects. Finally, we discuss how to innovate and standardize future neurofeedback clinical trials in epilepsy based on evidence from recent research studies.

Sleep and epilepsy: A clinical and pathophysiological overview.

The interaction between sleep and epilepsy is complex. A better understanding of the mechanisms linking sleep and epilepsy appears increasingly important as it may improve diagnosis and therapeutic strategies in patients with epilepsy. In this narrative review, we aim to (i) provide an overview of the physiological and pathophysiological processes linking sleep and epilepsy; (ii) present common sleep disorders in patients with epilepsy; (iii) discuss how sleep and sleep disorders should be considered in new therapeutic approaches to epilepsy such as neurostimulation; and (iv) present the overall nocturnal manifestations and differential diagnosis between epileptic seizures and parasomnia.

Vancomycin-resistant enterococci isolates colonizing and infecting haematology patients: clonality, and virulence and resistance profile.

BACKGROUND: Vancomycin-resistant enterococci (VRE) are an important agent of colonization and infection in haematology patients. However, the role of virulence on VRE colonization and infection is controversial. AIM: To characterize the lineage, virulence and resistance profile of VRE infection and colonization isolates; as well as their impact on outcome of haematology patients using a regression logistic model. METHODS: Eighty-six isolates (80 Enterococcus faecium and six E. faecalis) from 76 patients were evaluated. Polymerase chain reaction for resistance and virulence genes, and pulsed-field gel electrophoresis and whole genome sequencing of the major clusters, were performed. Bivariate and multivariate analyses were carried out to evaluate the role of virulence genes on outcome. FINDINGS: All isolates harboured the vanA gene. Regarding the virulence genes, 96.5% of isolates were positive for esp, 69.8% for gelE and asa1 genes. VRE infection isolates were more virulent than colonization isolates and harboured more often the gelE gene (P = 0.008). Infections caused by VRE carrying asa1 gene resulted more frequently in death (P = 0.004), but only the predominant clone remained as protector in the multivariate model. The E. faecium strains were assigned to seven STs (ST78, ST412, ST478, ST792, ST896, ST987, ST963) that belonged to CC17. The E. faecalis sequenced belonged to ST9 (CC9). CONCLUSION: E. faecium was predominant, and infection isolates were more virulent than colonization isolates and harboured more often the gene gelE. Infections caused by VRE carrying the asa1 gene appeared to be associated with a fatal outcome.

Full-scale phosphorus recovery from digested waste water sludge in Belgium - part I: technical achievements and challenges.

To date, phosphorus recovery as struvite in wastewater treatment plants has been mainly implemented on water phases resulting from dewatering processes of the sludge line. However, it is possible to recover struvite directly from sludge phases. Besides minimising the return loads of phosphorus from the sludge line to the water line, placing such a process within the sludge line is claimed to offer advantages such as a higher recovery potential, enhanced dewaterability of the treated sludge, and reduced speed of scaling in pipes and dewatering devices. In the wastewater treatment plant at Leuven (Belgium), a full-scale struvite recovery process from digested sludge has been tested for 1 year. Several monitoring campaigns and experiments provided indications of the efficiency of the process for recovery. The load of phosphorus from the sludge line returning to the water line as centrate accounted for 15% of the P-load of the plant in the reference situation. Data indicated that the process divides this phosphorus load by two. An improved dewaterability of 1.5% of dry solids content was achieved, provided a proper tuning of the installation. Quality analyses showed that the formed struvite was quite pure.

Influence of gravitational sympathetic stimulation on the Surgical Plethysmographic Index.

Surgical Plethysmographic Index (SPI), calculated from pulse photo-plethysmographic amplitude oscillations, has been proposed as a tool to measure nociception anti-nociception balance during general anesthesia, but it is affected by several confounding factor that alter the autonomic nervous system (ANS) modulation. We hypothesized that SPI may be mainly affected by sympathetic stimulation independently from nociception. We studied the effects of two sympathetic stimuli on SPI, delivered through passive head-up tilt at 45 and 90 degrees angles, in nine awake healthy adults. The sympathetic modulation was assessed by means of heart rate variability (HRV) analysis. Mean (SD) SPI significantly increased from baseline to 45 degrees [from 38.6 (13.7) to 60.8 (7.6), p<0.001)] and to 90 degrees angle tilt [82.3 (5.4), p<0.001]. The electrocardiographic mean R-to-R interval significantly shortened during both passive tilts, whereas systolic arterial pressure did not change during the study protocol. HRV changed significantly during the study protocol towards a predominance of sympathetic modulation during passive tilt. Gravitational sympathetic stimulation at two increasing angles, in absence of any painful stimuli, affects SPI in awake healthy volunteers. SPI seems to reflect the sympathetic outflow directed to peripheral vessels.

Surgical Pleth Index guided analgesia blunts the intraoperative sympathetic response to laparoscopic cholecystectomy.

BACKGROUND: Surgical noxious stimuli generate a stress response with an increased sympathetic activity, potentially affecting the perioperative outcome. Surgical Pleth Index (SPI), derived from the pulse plethysmogram, has been proposed as a tool to assess nociception-antinociception balance. The relationship between SPI and autonomic nervous system (ANS) during general anesthesia is poorly understood and it is doubtful if SPI-guided analgesia may offer advantages over the standard clinical practice. The study was designed to evaluate if SPI-guided analgesia leads to a lower sympathetic modulation compared with standard clinical practice. METHODS: Electrocardiographic wave, non-invasive blood pressure and SPI were recorded in ASA I-II patients undergoing elective laparoscopic cholecystectomy, randomized to receive SPI-guided analgesia or standard analgesia. Hemodynamic parameters, SPI, mean and variance of heart rate, low (LF) and high frequency (HF) spectral components of heart rate variability were measured at four time points: (T0) baseline, (T1) after induction of general anesthesia, (T2) after pneumoperitoneum insufflation and (T3) after pneumoperitoneum withdrawal. RESULTS: SPI, hemodynamic and ANS parameters changed significantly in both groups during the study period (P<0.0001). At T2 SPI and markers of sympathetic modulation were significantly lower in SPI group (mean [SD] SPI 38.1 [15.3] vs. 48.1 [16.2] normalized units, P<0.05; LF 38 [8.6] vs. 56.2 [20.6] normalized units, P<0.01; LF/HF 1.01 [1.1] vs. 2.68 [2.07], P<0.01). There was no difference in remifentanil consumption, recovery time from anesthesia, or postoperative pain and complications. CONCLUSION: SPI-guided analgesia led to a more stable sympathetic modulation but didn't seem to offer clinically relevant advantages over the standard clinical practice for laparoscopic cholecystectomy.

A new scale for the assessment of performance and capacity of hand function in children with hemiplegic cerebral palsy: reliability and validity studies.

BACKGROUND: In hemiplegic children, the recognition of the activity limitation pattern and the possibility of grading its severity are relevant for clinicians while planning interventions, monitoring results, predicting outcomes. OBJECTIVE: Aim of the study is to examine the reliability and validity of Besta Scale, an instrument used to measure in hemiplegic children from 18 months to 12 years of age both grasp on request (capacity) and spontaneous use of upper limb (performance) in bimanual play activities and in ADL. DESIGN: Psychometric analysis of reliability and of validity of the Besta scale was performed. SETTING: Outpatient study sample METHODS: Reliability study: A sample of 39 patients was enrolled. The administration of Besta scale was video-recorded in a standardized manner. All videos were scored by 20 independent raters on subsequent viewing. 3 raters randomly selected from the 20-raters group rescored the same video two years later for intra-rater reliability. Intra and inter-rater reliability were calculated using Intraclass Correlation Coefficient (ICC) and Kendall's coefficient (K), respectively. Internal consistency reliability was assessed using Alpha's Chronbach coefficient. Validity study: a sample of 105 children was assessed 5 times (at t0 and 2, 3, 6 and 12 months later) by 20 independent raters. Each patient underwent at the same time to QUEST and Besta scale administration and assessment. Criterion validity was calculated using rho-Pearson coefficient. RESULTS: Reliability study: The inter-rater reliability calculated with Kendall's coefficient resulted moderate K=0.47. The intra-rater (or test-retest) reliability for 3 raters was excellent (ICC=0.927). The Cronbach's alpha for internal consistency was 0.972. Validity study: Besta scale showed a good criterion validity compared to QUEST increasing by age and severity of impairment. Rho Pearson's correlation coefficient r was 0.81 (P<0.0001). Limitations. Besta scales in infants finds hard to distinguish between mild to moderately impaired hand function. CONCLUSIONS: Besta scale scoring system is a valid and reliable tool, utilizable in a clinical setting to monitor evolution of unimanual and bimanual manipulation and to distinguish hand's capacity from performance.

Oxytocin nasal spray in fibromyalgic patients.

Fibromyalgia is a pain disorder associated with frequent comorbid mood, anxiety, and sleep disorders. Despite the frequent use of a complex, poly-drug pharmacotherapy, treatment for fibromyalgia is of limited efficacy. Oxytocin has been reported to reduce the severity of pain, anxiety, and depression, and improve the quality of sleep, suggesting that it may be useful to treat fibromyalgia. To evaluate this hypothesis, 14 women affected by fibromyalgia and comorbid disorders, assuming a complex pharmacotherapy, were enrolled in a double-blind, crossover, randomized trial to receive oxytocin and placebo nasal spray daily for 3 weeks for each treatment. Order of treatment (placebo-oxytocin or oxytocin-placebo) was randomly assigned. Patients were visited once a week. At each visit, the following instruments were administered: an adverse drug reaction record card, Visual Analog Scale of Pain Intensity, Spielberger State Anxiety Inventory, Zung Self-rating Depression Scale, and SF-12. Women self-registered painkiller assumption, pain severity, and quality of sleep in a diary. Unlikely, oxytocin nasal spray (80 IU a day) did not induce positive therapeutic effects but resulted to be safe, devoid of toxicity, and easy to handle.

Lacosamide as add-on treatment of focal symptomatic epilepsy in a patient with alcoholic liver cirrhosis.

The occurrence of epileptic seizures in the presence of hepatic disease is not uncommon in clinical practice. Selecting an appropriate AED for patients affected by liver failure who have new-onset epileptic seizures can be challenging. We describe a 64-year-old man affected by liver cirrhosis. The patient developed partial epilepsy with secondary generalization because of an intracerebral hemorrhage in the left parieto-occipital regions. After the neurosurgery procedure, seizures reappeared and were initially managed with levetiracetam. After one month, the patient experienced clusters of seizures while on stable treatment with levetiracetam. Pregabalin as add-on was not tolerated; therefore, he received a low dose of phenobarbital as add-on treatment. The patient developed hepatic encephalopathy. Phenobarbital was immediately stopped, and oral lacosamide was added. A rapid recovery of encephalopathy with a 6-month seizure freedom was obtained. The patient died 6 months later because of progressive impairment of liver function. Lacosamide may represent an alternative to other AEDs in patients with liver failure; however, further prospective evaluation of its efficacy and safety in this clinical setting is needed.

Contrast-enhanced ultrasonography evaluation after autologous fat grafting in scar revision.

AIM: Fat transfer is commonly used to fill loss of volume in depressed scars caused by trauma, deep burns or surgery. The aim of the study is to investigate the degree of fat graft take through evaluation of the microcirculation of grafted autologous adipose tissue using contrast-enhanced ultrasonography. PATIENTS AND METHOD: From 2010 to 2012 at the Department of Plastic and Reconstructive Surgery of the Traumatological Center in Turin, a study population was selected from patients with surgical indications for autologous fat transfer for scar correction. For each surgical procedure patients underwent a clinical and sonographic evaluation before and after intervention (at 1 month and 3 months). RESULTS: Out of a total of 28 interventions, 24 showed a good result; defined as improvement of the scar, and confirmed by the presence of vascularization in the transplanted tissue. In 4 cases, there was a lack of blood supply at the first evaluation but an initial good clinical scar correction. The absence of blood vessels was confirmed at 3 months accompanied by complete resorption of the transferred fat with a failure of good clinical outcome. CONCLUSION: Contrast-enhanced ultrasonography was able to evaluate the microvasculature of adipose tissue after fat transfer. Due to this characteristic, it allows to monitor and predict the take of adipose tissue and provide realistic and early information on the clinical outcome of fat transfer.

K-nearest-neighbor conditional entropy approach for the assessment of the short-term complexity of cardiovascular control.

Complexity analysis of short-term cardiovascular control is traditionally performed using entropy-based approaches including corrective terms or strategies to cope with the loss of reliability of conditional distributions with pattern length. This study proposes a new approach aiming at the estimation of conditional entropy (CE) from short data segments (about 250 samples) based on the k-nearest-neighbor technique. The main advantages are: (i) the control of the loss of reliability of the conditional distributions with the pattern length without introducing a priori information; (ii) the assessment of complexity indexes without fixing the pattern length to an arbitrary low value. The approach, referred to as k-nearest-neighbor conditional entropy (KNNCE), was contrasted with corrected approximate entropy (CApEn), sample entropy (SampEn) and corrected CE (CCE), being the most frequently exploited approaches for entropy-based complexity analysis of short cardiovascular series. Complexity indexes were evaluated during the selective pharmacological blockade of the vagal and/or sympathetic branches of the autonomic nervous system. We found that KNNCE was more powerful than CCE in detecting the decrease of complexity of heart period variability imposed by double autonomic blockade. In addition, KNNCE provides indexes indistinguishable from those derived from CApEn and SampEn. Since this result was obtained without using strategies to correct the CE estimate and without fixing the embedding dimension to an arbitrary low value, KNNCE is potentially more valuable than CCE, CApEn and SampEn when the number of past samples most useful to reduce the uncertainty of future behaviors is high and/or variable among conditions and/or groups.

Short-term complexity indexes of heart period and systolic arterial pressure variabilities provide complementary information.

It is unclear whether the complexity of the variability of the systolic arterial pressure (SAP) provides complementary information to that of the heart period (HP). The complexity of HP and SAP variabilities was assessed from short beat-to-beat recordings (i.e., 256 cardiac beats). The evaluation was made during a pharmacological protocol that induced vagal blockade with atropine or a sympathetic blockade (beta-adrenergic blockade with propranolol or central sympathetic blockade with clonidine) alone or in combination, during a graded head-up tilt, and in patients with Parkinson's disease (PD) without orthostatic hypotension undergoing orthostatic challenge. Complexity was quantified according to the mean square prediction error (MSPE) derived from univariate autoregressive (AR) and multivariate AR (MAR) models. We found that: 1) MSPE(MAR) did not provide additional information to that of MSPE(AR); 2) SAP variability was less complex than that of HP; 3) because HP complexity was reduced by either vagal blockade or vagal withdrawal induced by head-up tilt and was unaffected by beta-adrenergic blockade, HP was under vagal control; 4) because SAP complexity was increased by central sympathetic blockade and was unmodified by either vagal blockade or vagal withdrawal induced by head-up tilt, SAP was under sympathetic control; 5) SAP complexity was increased in patients with PD; and 6) during orthostatic challenge, the complexity of both HP and SAP variabilities in patients with PD remained high, thus indicating both vagal and sympathetic impairments. Complexity indexes derived from short HP and SAP beat-to-beat series provide complementary information and are helpful in detecting early autonomic dysfunction in patients with PD well before circulatory symptoms become noticeable.

Circulation of West Nile virus lineage 1 and 2 during an outbreak in Italy.

In 2011, from 26 September to 16 October, a small outbreak of West Nile virus (WNV) disease occurred on the island of Sardinia (Italy). According to the national case definition, six cases with acute neurological disease were confirmed in hospitalized patients, and four of them died; one of these was only 34 years old. In two case, WNV RNA was detected in urine, suggesting renal involvement. Sequence analysis showed lineage 1 and 2 circulation.

Is target opioid therapy within sight?

Control of pain has a central role in patients treatment either in advanced cancer or other terminal illnesses and in acute postsurgical or chronic non-malignant diseases. Hospitals should promote programs of research on genetic mechanism, and also biochemical and physiological aspects of pain through highly specialized labs. Opioids are the first choice drugs for moderate to severe chronic pain, especially at the end of life, and among them oral morphine is worldwide recognized by the World Health Organization and by the European Association for Palliative Care as the conventional therapy. Although this general agreement, administration of this class of drugs may be a major medical challenge due to the high effects' variability related to pharmacokinetic and pharmacodynamic parameters, such as absorption, distribution and metabolism, as well as intrinsic efficacy at the receptors involved. For such a reason, optimization of the management regime is not always reached in all the patients. Up to now no one can easily predict which patient will experience side effects or an inadequate pain control. The growing body of evidence concerning a sound genetic background of this human intervariability has prompted research on the field of a personalized therapy, focusing on single nucleotide polymorphisms (SNPs), being the most common and diffuse form of genetic variation. This review has the main goal to report the most promising human genetic polymorphisms involved in opioid treatment, and address the relationship between these polymorphisms and the clinical outcome.

Gait pattern classification in children with Charcot-Marie-Tooth disease type 1A.

Gait pattern classification may assist in clinical decision making and cluster analysis (CA) has been often adopted to this aim. The goal of this study was to identify, through CA, typical walking patterns in a group of 21 young subjects with CMT1A, a hereditary progressive neuropathy, and to study possible correlation with the disease's clinical status. The protocol included kinematic/kinetic analysis of natural walking and more demanding locomotor tasks, i.e. toe- and heel-walking. Hierarchical cluster analysis was carried out on parameters related to primary signs (foot-drop and push-off deficit) and, separately, to compensatory mechanisms at proximal (pelvis, hip and knee) or distal (ankle) level. CA on primary signs during natural walking identified three clusters: (1) pseudo-normal patients (PN), not significantly different from controls; (2) patients showing only foot-drop (FD); (3) patients with foot-drop and push-off deficit (FD&POD). Patients belonging to the PN subgroup showed distal abnormalities during heel-walking. The FD&POD subgroup was associated to a significantly worse clinical score (CMTES, p<0.05). The main compensatory strategies, which occurred independently from primary clusterization, included augmented hip/knee flexion in swing (steppage) and early ankle plantarflexion at mid stance (vaulting). We concluded that, although a number of young CMT1A patients do not show typical primary deviations during natural walking, they do show significant abnormalities in more demanding locomotor tasks that should be therefore considered. It is also hypothesized that progression of this degenerative condition may be associated to the migration of patients to more severe clusters, with possible appearance of compensatory strategies.

Serological evidence of Toscana virus infection in Portuguese patients.

Toscana virus (TOSV) is an emerging Phlebovirus of growing interest as a human pathogen in the Mediterranean Basin. In Portugal, however, little is known about the prevalence of TOSV infection. The aim of this work was to perform a seroprevalence study in patients with requests for laboratory diagnosis of vector-borne viruses. A total of 538 patients with and without neurological signs from 2004 to 2008 were studied by in-house indirect immunofluorescence assay and commercial enzyme-linked immunosorbent assays. A prevalence of 4.2% for IgG antibodies was found in the group of patients with neurological signs. Five (3%) of these had recent infections. In the group with no neurological signs, the IgG prevalence was 1.3%. Two samples, belonging to two patients, were also confirmed with plaque reduction neutralization tests with the TOSV ISS. Phl.3 Italian strain. This work showed that TOSV is present and causing disease from north to south in Portugal. The probable circulation of different phlebovirus serotypes in Portugal emphasizes the need for further studies.

Prevalence of antibodies to phleboviruses and flaviviruses in Peja, Kosovo.

In order to investigate the current and past activity of phlebovirus and flavivirus in Kosovo, a seroprevalence study among 200 blood donors was performed. Positive results were obtained for the phleboviruses TOSV and SFNV, and for a flavivirus of the Japanese Encephalitis group. No positive results for TBEV were observed.

Reliability of instrumented movement analysis as outcome measure in Charcot-Marie-Tooth disease: results from a multitask locomotor protocol.

Some neurodegenerative diseases at early stage may not drastically affect basic gait ability, whereas more demanding locomotor tasks are more prone to disease-induced abnormalities. In this study, we evaluated the interday test-retest reliability, 4-6 weeks apart, of instrumented movement analysis on a group of 20 subjects with Charcot-Marie-Tooth (CMT) disease considering a set of kinematic and kinetic curves and related parameters obtained during natural walking (NW) and faster walking, heel and toe-walking, step ascending and descending. Results showed that the reliability was good for NW, with the exception of trunk curves, pelvic tilt and EMG profiles (moderate reliability), and trunk ROM in sagittal/transverse plane (poor reliability). Comparing our results with literature, CMT patients did not present a greater variability during NW than healthy subjects or patients with diseases of CNS. Additional locomotor tasks showed a slight reduction of reliability, although the moderate-to-good level shown in NW was almost never reduced to poor. Most of SEM values (absolute measurement errors) were smaller than 5°, a clinically acceptable threshold. In particular THS, an ankle joint related parameter computed across heel and toe-walking tasks, showed an optimal reliability (ICC=0.95, SEM=2.7°) and correlation with CMT clinical scores. Toe and heel-walking and step ascending tasks maximised the number of parameters with a moderate-to-good correlation with patients' clinical status. We concluded that, in addition to natural walking, more challenging locomotor tasks are good candidates to provide reliable and sensitive outcome measures for CMT patients.

Study of neurinomas with ultrasound contrast media: review of a case series to identify characteristic imaging patterns.

PURPOSE: The aim of this study was to evaluate whether there exists a characteristic distribution pattern of vessels within neurinomas that may be used to characterise this type of lesion by employing a contrast-specific ultrasound technique. MATERIALS AND METHODS: Between January 2003 and May 2010, 66 suspected neurinomas were evaluated according to their sonographic features (solid fusiform mass with well-defined margins located in direct continuity with the nerve that was not always discernible and heterogeneous as a result of the presence of small cystic areas or calcifications). The lesions were examined using a sonographic contrast medium consisting of sulphur hexafluoride microbubbles and equipment with dedicated contrast-specific software [contrast tuned imaging (CnTI)]. Of these lesions, five were excluded from the analysis because the definitive diagnosis was not available (in two cases, the follow-up was still in progress, whereas in the remaining three, there was no follow-up). Our study, therefore, is based on 61 surgically excised lesions that were confirmed to be neurinomas by histology, which is regarded as the gold standard. RESULTS: In 41/61 cases (67.2%), we identified an enhancement pattern that we termed reticular owing to the interweaving of blood vessels, of which two subtypes were identified depending on whether the interwoven vessels were densely or sparsely packed: loose-knit reticular in 18/41, and tight-knit reticular in 23/41. In 20/61 (32.8%) cases, we observed a vascular pattern of diffuse heterogeneous enhancement, which was divided into two subtypes based on the presence of one (7/20) or more (13/20) avascular areas. CONCLUSIONS: Results showed that all neurinomas studied could be divided into two groups according to the type of enhancement pattern observed: reticular or diffuse heterogeneous.