Diverging cell wall strategies for drought adaptation in two maize inbreds with contrasting lodging resistance.

The plant cell wall is a plastic structure of variable composition that constitutes the first line of defence against environmental challenges. Lodging and drought are two stressful conditions that severely impact maize yield. In a previous work, we characterised the cell walls of two maize inbreds, EA2024 (susceptible) and B73 (resistant) to stalk lodging. Here, we show that drought induces distinct phenotypical, physiological, cell wall, and transcriptional changes in the two inbreds, with B73 exhibiting lower tolerance to this stress than EA2024. In control conditions, EA2024 stalks had higher levels of cellulose, uronic acids and p-coumarate than B73. However, upon drought EA2024 displayed increased levels of arabinose-enriched polymers, such as pectin-arabinans and arabinogalactan proteins, and a decreased lignin content. By contrast, B73 displayed a deeper rearrangement of cell walls upon drought, including modifications in lignin composition (increased S subunits and S/G ratio; decreased H subunits) and an increase of uronic acids. Drought induced more substantial changes in gene expression in B73 compared to EA2024, particularly in cell wall-related genes, that were modulated in an inbred-specific manner. Transcription factor enrichment assays unveiled inbred-specific regulatory networks coordinating cell wall genes expression. Altogether, these findings reveal that B73 and EA2024 inbreds, with opposite stalk-lodging phenotypes, undertake different cell wall modification strategies in response to drought. We propose that the specific cell wall composition conferring lodging resistance to B73, compromises its cell wall plasticity, and renders this inbred more susceptible to drought.

A novel pectin methylesterase inhibitor, PMEI3, in common bean suggests a key role of pectin methylesterification in Pseudomonas resistance.

The mechanisms underlying susceptibility to and defense against Pseudomonas syringae (Pph) of the common bean (Phaseolus vulgaris) have not yet been clarified. To investigate these, 15-day-old plants of the variety Riñón were infected with Pph and the transcriptomic changes at 2 h and 9 h post-infection were analysed. RNA-seq analysis showed an up-regulation of genes involved in defense/signaling at 2 h, most of them being down-regulated at 9 h, suggesting that Pph inhibits the transcriptomic reprogramming of the plant. This trend was also observed in the modulation of 101 cell wall-related genes. Cell wall composition changes at early stages of Pph infection were associated with homogalacturonan methylation and the formation of egg boxes. Among the cell wall genes modulated, a pectin methylesterase inhibitor 3 (PvPMEI3) gene, closely related to AtPMEI3, was detected. PvPMEI3 protein was located in the apoplast and its pectin methylesterase inhibitory activity was demonstrated. PvPMEI3 seems to be a good candidate to play a key role in Pph infection, which was supported by analysis of an Arabidopsis pmei3 mutant, which showed susceptibility to Pph, in contrast to resistant Arabidopsis Col-0 plants. These results indicate a key role of the degree of pectin methylesterification in host resistance to Pph during the first steps of the attack.

Optical coherence tomography for the screening of anterior chamber inflammation in paediatric patients diagnosed with juvenile idiopathic arthritis.

OBJECTIVES: To evaluate the effectiveness of the anterior segment optical coherence tomography (AS-OCT) for the screening of anterior uveitis in children diagnosed with juvenile idiopathic arthritis (JIA). METHODS: A cross-sectional, observational, non-randomised study was conducted in JIA patients younger than 18 years. All patients underwent anterior segment (AS-OCT) and macular OCT. RESULTS: A total of 300 eyes of 150 patients diagnosed with JIA were included; 74% were females, and mean age was 11.12 ± 3.51 years old (range 4.13-18.60). In the slit-lamp examination, anterior uveitis was diagnosed in 16 eyes. In the AS-OCT, anterior uveitis was suspected in 27 eyes; cells were detected in 27 eyes and retrokeratic precipitates in 5 eyes. Sensitivity was 0.94 and specificity was 0.96, positive predictive value was 0.59 and negative predictive value was 0.99, and Kappa-Cohen index was 0.71. CONCLUSIONS: AS-OCT could be considered for the screening of anterior segment uveitis in children diagnosed with JIA.

Disorganization of language and working memory systems in frontal versus temporal lobe epilepsy.

Cognitive impairment is a common comorbidity of epilepsy and adversely impacts people with both frontal lobe (FLE) and temporal lobe (TLE) epilepsy. While its neural substrates have been investigated extensively in TLE, functional imaging studies in FLE are scarce. In this study, we profiled the neural processes underlying cognitive impairment in FLE and directly compared FLE and TLE to establish commonalities and differences. We investigated 172 adult participants (56 with FLE, 64 with TLE and 52 controls) using neuropsychological tests and four functional MRI tasks probing expressive language (verbal fluency, verb generation) and working memory (verbal and visuo-spatial). Patient groups were comparable in disease duration and anti-seizure medication load. We devised a multiscale approach to map brain activation and deactivation during cognition and track reorganization in FLE and TLE. Voxel-based analyses were complemented with profiling of task effects across established motifs of functional brain organization: (i) canonical resting-state functional systems; and (ii) the principal functional connectivity gradient, which encodes a continuous transition of regional connectivity profiles, anchoring lower-level sensory and transmodal brain areas at the opposite ends of a spectrum. We show that cognitive impairment in FLE is associated with reduced activation across attentional and executive systems, as well as reduced deactivation of the default mode system, indicative of a large-scale disorganization of task-related recruitment. The imaging signatures of dysfunction in FLE are broadly similar to those in TLE, but some patterns are syndrome-specific: altered default-mode deactivation is more prominent in FLE, while impaired recruitment of posterior language areas during a task with semantic demands is more marked in TLE. Functional abnormalities in FLE and TLE appear overall modulated by disease load. On balance, our study elucidates neural processes underlying language and working memory impairment in FLE, identifies shared and syndrome-specific alterations in the two most common focal epilepsies and sheds light on system behaviour that may be amenable to future remediation strategies.

Cognitive phenotype of juvenile absence epilepsy: An investigation of patients and unaffected siblings.

OBJECTIVE: The cognitive profile of juvenile absence epilepsy (JAE) remains largely uncharacterized. This study aimed to: (1) elucidate the neuropsychological profile of JAE; (2) identify familial cognitive traits by investigating unaffected JAE siblings; (3) establish the clinical meaningfulness of JAE-associated cognitive traits; (4) determine whether cognitive traits across the idiopathic generalized epilepsy (IGE) spectrum are shared or syndrome-specific, by comparing JAE to juvenile myoclonic epilepsy (JME); and (5) identify relationships between cognitive abilities and clinical characteristics. METHODS: We investigated 123 participants-23 patients with JAE, 16 unaffected siblings of JAE patients, 45 healthy controls, and 39 patients with JME-who underwent a comprehensive neuropsychological test battery including measures within four cognitive domains: attention/psychomotor speed, language, memory, and executive function. We correlated clinical measures with cognitive performance data to decode effects of age at onset and duration of epilepsy. RESULTS: Cognitive performance in individuals with JAE was reduced compared to controls across attention/psychomotor speed, language, and executive function domains; those with ongoing seizures additionally showed lower memory scores. Patients with JAE and their unaffected siblings had similar language impairment compared to controls. Individuals with JME had worse response inhibition than those with JAE. Across all patients, those with older age at onset had better attention/psychomotor speed performance. SIGNIFICANCE: JAE is associated with wide-ranging cognitive difficulties that encompass domains reliant on frontal lobe processing, including language, attention, and executive function. JAE siblings share impairment with patients on linguistic measures, indicative of a familial trait. Executive function subdomains may be differentially affected across the IGE spectrum. Cognitive abilities are detrimentally modulated by an early age at seizure onset.

Camera-based Prospective Motion Correction in Paediatric Epilepsy Patients Enables EEG-fMRI Localization Even in High-motion States.

BACKGROUND: EEG-fMRI is a useful additional test to localize the epileptogenic zone (EZ) particularly in MRI negative cases. However subject motion presents a particular challenge owing to its large effects on both MRI and EEG signal. Traditionally it is assumed that prospective motion correction (PMC) of fMRI precludes EEG artifact correction. METHODS: Children undergoing presurgical assessment at Great Ormond Street Hospital were included into the study. PMC of fMRI was done using a commercial system with a Moiré Phase Tracking marker and MR-compatible camera. For retrospective EEG correction both a standard and a motion educated EEG artefact correction (REEGMAS) were compared to each other. RESULTS: Ten children underwent simultaneous EEG-fMRI. Overall head movement was high (mean RMS velocity < 1.5 mm/s) and showed high inter- and intra-individual variability. Comparing motion measured by the PMC camera and the (uncorrected residual) motion detected by realignment of fMRI images, there was a five-fold reduction in motion from its prospective correction. Retrospective EEG correction using both standard approaches and REEGMAS allowed the visualization and identification of physiological noise and epileptiform discharges. Seven of 10 children had significant maps, which were concordant with the clinical EZ hypothesis in 6 of these 7. CONCLUSION: To our knowledge this is the first application of camera-based PMC for MRI in a pediatric clinical setting. Despite large amount of movement PMC in combination with retrospective EEG correction recovered data and obtained clinically meaningful results during high levels of subject motion. Practical limitations may currently limit the widespread use of this technology.

Epidermolysis bullosa acquisita: a case series of three paediatric patients.

Epidermolysis bullosa acquisita is a highly uncommon condition in the paediatric population. This article describes three children with this disease, different clinical presentation and management. It also reviews the most relevant articles on this topic.

Epilepsy and lockdown: A survey of patients normally attending a Spanish centre.

BACKGROUND: Lockdown due to the SARS-CoV-2 pandemic became a challenge to maintain care for patients with epilepsy; we aimed to find out how the pandemic affected them. METHODS: We sent an online 22-item questionnaire to patients from our outpatient clinic, a reference centre in Spain for drug-resistant epilepsy, inquiring about the effects of lockdown, from March to May 2020. RESULTS: We sent the survey to 627 patients; 312 (58% women) sent a complete response and were included. Of all respondents, 57% took >2 antiseizure medications. One-third of respondents (29%) declared an associated cognitive or motor disability. A minority had confirmed infection with SARS-CoV-2 (1.92%). Seizure frequency remained like usual in 56% of patients, while 31.2% reported an increase. Less than 10% needed emergent assistance. Almost half reported anxiety or depression, and 25% increased behavioural disorders. Mood (F: 5.40; p: 0.002) and sleep disorders (F = 2.67; p: 0.05) were associated with increase in seizure frequency. Patients were able to contact their physicians when needed and were open to a future telematic approach to follow-up visits. CONCLUSIONS: Seizure frequency and severity remained unchanged in most patients during the lockdown. Mood and sleep disorders were common and associated with seizure worsening. Patients were open to telematic care in the future.

Psychiatric disorders in patients with resistant temporal lobe epilepsy two years after undergoing elective surgery. A longitudinal study.

PURPOSE: Psychiatric morbidity in temporal lobe epilepsy (TLE) is frequent and negatively affects patients' life quality. Surgery is the procedure of choice when treating seizures, although the effects on psychiatric disorders remain unclear. We evaluate the effect of surgery on psychiatric disorders in patients with TLE two years after the intervention, to then shed light on how these are related to anxiety and depression symptoms, and Interictal Dysphoric Disorder (IDD). METHODS: We included data from 65 patients with TLE whose psychiatric evaluations were performed according to DSM-IV criteria. Anxiety and depression symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS) test. RESULTS: At 2-year follow-up, anxiety and depressive disorders decreased, and psychotic disorders augmented without statistical significance. Baseline psychiatric disorders predisposed to psychiatric pathology at 2-year follow-up and did not correlate with epilepsy outcome after surgery. Postoperative psychiatric disorders correlated with the seizure incidence two years after the intervention, suggesting that epilepsy and psychiatric disorders were associated in processes such as surgery. De novo psychiatric disorders represented 52% of postoperative psychiatric pathology, 62% being psychotic disorders. De novo psychiatric disorders became more frequent from the first year of surgery, occurring mainly in patients free of seizures. The HADS test scores and IDD correlated with psychiatric disorders at 2-year follow-up. CONCLUSIONS: Baseline psychiatric disorders did not influence surgery outcome, but correlated with psychiatric disorders' prevalence two years after surgery. Despite not finding statistical significance, surgery reduced the prevalence of psychiatric disorders, and de novo psychiatric disorders were associated with an improvement in the epilepsy course at 2-year follow-up.

Relationship between sleep quality and cognitive performance in patients with epilepsy.

PURPOSE: To investigate the relationship between self-reported sleep quality and cognitive function in patients with epilepsy (PWE), as well as anxiety and depressive symptoms and patient quality of life (QoL). METHODS: This multicenter cross-sectional study included PWE aged ≥12 years who were receiving ≥1 anti-seizure medication (ASM) and had not been diagnosed with a sleep disorder. Patients completed the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Montreal Cognitive Assessment test (MoCA), the Hospital Anxiety and Depression Scale (HADS), and the Quality of Life in Epilepsy Inventory-10 (QOLIE-10). RESULTS: The study enrolled 150 patients aged 16-83 years, mean age (standard deviation [SD]) 40.6 (15.2) years; 58.7% were female and 75.3% had focal epilepsy. Mean (SD) PSQI score was 4.71 (3.08), 44.4% of patients had impaired sleep quality (PSQI score ≥5), 19.9% had pathologic excessive daytime sleepiness (ESS score >12), and 32.7% had mild cognitive impairment (MoCA score <26). Within the PSQI, sleep disturbance (P = 0.036) and use of sleep medication (P = 0.006) scores were significantly higher in patients with mild cognitive impairment. Multiple regression analysis showed older age (regression coefficient [B], -0.086; 95% confidence interval [CI], -0.127, -0.045; P < 0.001) and the use of sleep medication component of the PSQI [B, -1.157; 95% CI, -2.064, -0.220; P = 0.013) were independently associated with lower MoCA score. Poor sleep quality was associated with probable anxiety and depression symptoms, and directly correlated with reduced QoL. CONCLUSIONS: In PWE, sleep quality was not significantly independently associated with mild cognitive impairment, although poor sleep quality had a negative effect on mood and QoL.

Perception and First Defense Responses Against Pseudomonas syringae pv. phaseolicola in Phaseolus vulgaris: Identification of Wall-Associated Kinase Receptors.

Common bean (Phaseolus vulgaris) is attacked by several pathogens such as the biotrophic gamma-proteobacterium Pseudomonas syringae pv. phaseolicola. To study the P. syringae pv. phaseolicola-bean interaction during the first stages of infection, leaf discs of a susceptible bean cultivar Riñón were infected with pathogenic P. syringae pv. phaseolicola. Using this experimental system, we tested six new putative wall-associated kinase (WAK) receptors, previously identified in silico. These six P. vulgaris WAKs (PvWAKs) showed high protein sequence homology to the well-described Arabidopsis thaliana WAK1 (AtWAK1) receptor and, by phylogenetic analysis, clustered together with AtWAKs. The expression of PvWAK1 increased at very early stages after the P. syringae pv. phaseolicola infection. Time course experiments were performed to evaluate the accumulation of apoplastic H2O2, Ca2+ influx, total H2O2, antioxidant enzymatic activities, lipid peroxidation, and the concentrations of abscisic acid and salicylic acid (SA), as well as the expression of six defense-related genes: MEKK-1, MAPKK, WRKY33, RIN4, PR1, and NPR1. The results showed that overexpression of PR1 occurred 2 h after P. syringae pv. phaseolicola infection without a concomitant increase in SA levels. Although apoplastic H2O2 increased after infection, the oxidative burst was neither intense nor rapid, and an efficient antioxidant response did not occur, suggesting that the observed cellular damage was caused by the initial increase in total H2O2 early after infection. In conclusion, Riñón can perceive the presence of P. syringae pv. phaseolicola, but this recognition results in only a modest and slow activation of host defenses, leading to high susceptibility to P. syringae pv. phaseolicola.

The emerging role of the advanced practice epilepsy nurse: A comparative study between two countries.

AIMS AND OBJECTIVES: The aim of the study was to compare advanced practice in epilepsy nurses in Spain and United Kingdom, identifying differences in the domains of standard advanced practice. BACKGROUND: Europe has recently faced the challenge of providing high-quality care for patients with epilepsy, a disease that generates many health demands. In some countries, such as the United Kingdom, advanced practice nursing is well established and could serve as a guide for implantation in countries where it is still in development, as is the case of Spain. DESIGN: A multicentre cross-sectional descriptive cohort study compared differences in the roles of advanced practice nurses in Spain and the United Kingdom. METHODS: The Advanced Practice Role Delineation Tool and its validated Spanish version were administered using an online questionnaire in a cohort of advanced practice epilepsy nurses in both countries. A convenience sample was recruited between January to December 2019. The study complied with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. RESULTS: Most United Kingdom nurses in our sample came from community environments, in contrast to Spanish nurses who worked in hospital. All domains analysed in the survey had significantly higher scores in the United Kingdom than in the Spanish cohort, especially in the research and leadership domains. CONCLUSIONS: The advanced practice role in Spain is underdeveloped compared with the United Kingdom. Differences in the settings of advanced roles in epilepsy nurses may be explained by greater community practice in the United Kingdom and differences in organisational and health systems. RELEVANCE TO CLINICAL PRACTICE: Our study showed the need to implement specific policies to develop advance practice nurse roles in Spain to improve the quality of care of patients with epilepsy.

[Flaccid paralysis and abdominal pain, an approach to porphyrias: a literature review and case series]. / Dolor abdominal y parálisis flácida, una aproximación a las porfirias: serie de casos y revisión de la literatura.

Porphyrias are inherited metabolic disorders caused by enzymatic deficiencies of HEM group biosynthesis. Most common in childhood at the third and fourth decade of life. They are characterized by increased levels of porphyrins, and various cutaneous, neurological, and visceral manifestations. We describe a series of 3 cases of female patients in the third decade of life with abdominal pain and a wide range of clinical manifestations and short and long-term complications. Our review contributes to the early recognition of these diseases to establish early specific managements to impact on irreversible outcomes.

Motor hyperactivation during cognitive tasks: An endophenotype of juvenile myoclonic epilepsy.

OBJECTIVE: Juvenile myoclonic epilepsy (JME) is the most common genetic generalized epilepsy syndrome. Myoclonus may relate to motor system hyperexcitability and can be provoked by cognitive activities. To aid genetic mapping in complex neuropsychiatric disorders, recent research has utilized imaging intermediate phenotypes (endophenotypes). Here, we aimed to (a) characterize activation profiles of the motor system during different cognitive tasks in patients with JME and their unaffected siblings, and (b) validate those as endophenotypes of JME. METHODS: This prospective cross-sectional investigation included 32 patients with JME, 12 unaffected siblings, and 26 controls, comparable for age, sex, handedness, language laterality, neuropsychological performance, and anxiety and depression scores. We investigated patterns of motor system activation during episodic memory encoding and verb generation functional magnetic resonance imaging (fMRI) tasks. RESULTS: During both tasks, patients and unaffected siblings showed increased activation of motor system areas compared to controls. Effects were more prominent during memory encoding, which entailed hand motion via joystick responses. Subgroup analyses identified stronger activation of the motor cortex in JME patients with ongoing seizures compared to seizure-free patients. Receiver-operating characteristic curves, based on measures of motor activation, accurately discriminated both patients with JME and their siblings from healthy controls (area under the curve: 0.75 and 0.77, for JME and a combined patient-sibling group against controls, respectively; P < .005). SIGNIFICANCE: Motor system hyperactivation represents a cognitive, domain-independent endophenotype of JME. We propose measures of motor system activation as quantitative traits for future genetic imaging studies in this syndrome.

Abnormal hippocampal structure and function in juvenile myoclonic epilepsy and unaffected siblings.

Juvenile myoclonic epilepsy is the most common genetic generalized epilepsy syndrome, characterized by a complex polygenetic aetiology. Structural and functional MRI studies demonstrated mesial or lateral frontal cortical derangements and impaired fronto-cortico-subcortical connectivity in patients and their unaffected siblings. The presence of hippocampal abnormalities and associated memory deficits is controversial, and functional MRI studies in juvenile myoclonic epilepsy have not tested hippocampal activation. In this observational study, we implemented multi-modal MRI and neuropsychological data to investigate hippocampal structure and function in 37 patients with juvenile myoclonic epilepsy, 16 unaffected siblings and 20 healthy controls, comparable for age, gender, handedness and hemispheric dominance as assessed with language laterality indices. Automated hippocampal volumetry was complemented by validated qualitative and quantitative morphological criteria to detect hippocampal malrotation, assumed to represent a neurodevelopmental marker. Neuropsychological measures of verbal and visuo-spatial learning and an event-related verbal and visual memory functional MRI paradigm addressed mesiotemporal function. We detected a reduction of mean left hippocampal volume in patients and their siblings compared with controls (P < 0.01). Unilateral or bilateral hippocampal malrotation was identified in 51% of patients and 50% of siblings, against 15% of controls (P < 0.05). For bilateral hippocampi, quantitative markers of verticalization had significantly larger values in patients and siblings compared with controls (P < 0.05). In the patient subgroup, there was no relationship between structural measures and age at disease onset or degree of seizure control. No overt impairment of verbal and visual memory was identified with neuropsychological tests. Functional mapping highlighted atypical patterns of hippocampal activation, pointing to abnormal recruitment during verbal encoding in patients and their siblings [P < 0.05, familywise error (FWE)-corrected]. Subgroup analyses indicated distinct profiles of hypoactivation along the hippocampal long axis in juvenile myoclonic epilepsy patients with and without malrotation; patients with malrotation also exhibited reduced frontal recruitment for verbal memory, and more pronounced left posterior hippocampal involvement for visual memory. Linear models across the entire study cohort indicated significant associations between morphological markers of hippocampal positioning and hippocampal activation for verbal items (all P < 0.05, FWE-corrected). We demonstrate abnormalities of hippocampal volume, shape and positioning in patients with juvenile myoclonic epilepsy and their siblings, which are associated with reorganization of function and imply an underlying neurodevelopmental mechanism with expression during the prenatal stage. Co-segregation of abnormal hippocampal morphology in patients and their siblings is suggestive of a genetic imaging phenotype, independent of disease activity, and can be construed as a novel endophenotype of juvenile myoclonic epilepsy.

Emergency implementation of telemedicine for epilepsy in Spain: Results of a survey during SARS-CoV-2 pandemic.

Teleneurology in Spain had not been implemented so far in clinical practice, except in urgent patients with stroke. Telemedicine was hardly used in epilepsy, and patients and neurologists usually preferred onsite visits. Our goal was to study impressions of adult and pediatric epileptologists about the use of telemedicine after emergent implementation during the new coronavirus 2019 (COVID-19) pandemic. METHODS: An online survey was sent to the members of the Spanish Epilepsy Society and the members of the Epilepsy Study Group of the Catalan Neurological Society, inquiring about different aspects of telemedicine in epilepsy during the pandemic lockdown. RESULTS: A total of 66 neurologists responded, mostly adult neurologists (80.3%), the majority with a monographic epilepsy clinic (4 out of 5). Of all respondents, 59.1% reported to attend more than 20 patients with epilepsy (PWE) a week. During the pandemic, respondents handled their epilepsy clinics mainly with telephone calls (88%); only 4.5% used videoconference. Changes in antiseizure medications were performed less frequently than during onsite visits by 66.6% of the epileptologists. Scales were not administered during these visits, and certain types of information such as sudden expected unrelated death in epilepsy (SUDEP) were felt to be more appropriate to discuss in person. More than 4 out of 5 of the neurologists (84.8%) stated that they would be open to perform some telematic visits in the future. CONCLUSIONS: In Spain, emergent implantation of teleneurology has shown to be appropriate for the care of many PWE. Technical improvements, extended use of videoconference and patient selection may improve results and patient and physician satisfaction.

Patient opinion of analgesia during external cephalic version at term in singleton pregnancy.

To assess the opinion and the level of satisfaction of patients concerning analgesia during external cephalic version (ECV), we present the results of a survey of 120 women undergoing ECV at term during a randomised controlled trial (July 2012 to February 2013) comparing remifentanil and nitrous oxide. Overall, 110 (91.7%) women said they would repeat the procedure and 111 (92.5%) that they would recommend it to another pregnant woman, with no significant differences by type of analgesia. The administration and sense of comfort were rated better in the remifentanil group (p < .01). In conclusion, the use of analgesia during ECV is associated with a high rate of willingness among women to repeat the procedure and recommend it to other pregnant women.Impact statementWhat is already known on this subject? ECV is commonly a painful manoeuvre for the woman. This pain triggers maternal reactive abdominal muscle contraction and involuntary abdominal tensing, reducing the likelihood of successful version and causing some women to reject the technique.What do the results of this study add? The use of analgesia during ECV is associated with a high rate of willingness among women to repeat the procedure and recommend it to other pregnant women. The sense of comfort during ECV was also significantly better in the remifentanil group, probably because of its greater analgesic power and greater comfort during its administration.What are the implications of these findings for clinical practice and/or further research? ECV should be carried out under analgesia, when available, not only to decrease pain but also to encourage wider adoption of the technique and enable more women to benefit from it.

BOLD mapping of human epileptic spikes recorded during simultaneous intracranial EEG-fMRI: The impact of automated spike classification.

OBJECTIVES: Simultaneous intracranial EEG and functional MRI (icEEG-fMRI) can be used to map the haemodynamic (BOLD) changes associated with the generation of IEDs. Unlike scalp EEG-fMRI, in most patients who undergo icEEG-fMRI, IEDs recorded intracranially are numerous and show variability in terms of field amplitude and morphology. Therefore, visual marking can be highly subjective and time consuming. In this study, we applied an automated spike classification algorithm, Wave_clus (WC), to IEDs marked visually on icEEG data acquired during simultaneous fMRI acquisition. The motivation of this work is to determine whether using a potentially more consistent and unbiased automated approach can produce more biologically meaningful BOLD patterns compared to the BOLD patterns obtained based on the conventional, visual classification. METHODS: We analysed simultaneous icEEG-fMRI data from eight patients with severe drug resistant epilepsy, and who subsequently underwent resective surgery that resulted in a good outcome: confirmed epileptogenic zone (EZ). For each patient two fMRI analyses were performed: one based on the conventional visual IED classification and the other based on the automated classification. We used the concordance of the IED-related BOLD maps with the confirmed EZ as an indication of their biological meaning, which we compared for the automated and visual classifications for all IED originating in the EZ. RESULTS: Across the group, the visual and automated classifications resulted in 32 and 24 EZ IED classes respectively, for which 75% vs 83% of the corresponding BOLD maps were concordant. At the single-subject level, the BOLD maps for the automated approach had greater concordance in four patients, and less concordance in one patient, compared to those obtained using the conventional visual classification, and equal concordance for three remaining patients. These differences did not reach statistical significance. CONCLUSION: We found automated IED classification on icEEG data recorded during fMRI to be feasible and to result in IED-related BOLD maps that may contain similar or greater biological meaning compared to the conventional approach in the majority of the cases studied. We anticipate that this approach will help to gain significant new insights into the brain networks associated with IEDs and in relation to postsurgical outcome.

Dynamic brain network states in human generalized spike-wave discharges.

Generalized spike-wave discharges in idiopathic generalized epilepsy are conventionally assumed to have abrupt onset and offset. However, in rodent models, discharges emerge during a dynamic evolution of brain network states, extending several seconds before and after the discharge. In human idiopathic generalized epilepsy, simultaneous EEG and functional MRI shows cortical regions may be active before discharges, and network connectivity around discharges may not be normal. Here, in human idiopathic generalized epilepsy, we investigated whether generalized spike-wave discharges emerge during a dynamic evolution of brain network states. Using EEG-functional MRI, we studied 43 patients and 34 healthy control subjects. We obtained 95 discharges from 20 patients. We compared data from patients with discharges with data from patients without discharges and healthy controls. Changes in MRI (blood oxygenation level-dependent) signal amplitude in discharge epochs were observed only at and after EEG onset, involving a sequence of parietal and frontal cortical regions then thalamus (P < 0.01, across all regions and measurement time points). Examining MRI signal phase synchrony as a measure of functional connectivity between each pair of 90 brain regions, we found significant connections (P < 0.01, across all connections and measurement time points) involving frontal, parietal and occipital cortex during discharges, and for 20 s after EEG offset. This network prominent during discharges showed significantly low synchrony (below 99% confidence interval for synchrony in this network in non-discharge epochs in patients) from 16 s to 10 s before discharges, then ramped up steeply to a significantly high level of synchrony 2 s before discharge onset. Significant connections were seen in a sensorimotor network in the minute before discharge onset. This network also showed elevated synchrony in patients without discharges compared to healthy controls (P = 0.004). During 6 s prior to discharges, additional significant connections to this sensorimotor network were observed, involving prefrontal and precuneus regions. In healthy subjects, significant connections involved a posterior cortical network. In patients with discharges, this posterior network showed significantly low synchrony during the minute prior to discharge onset. In patients without discharges, this network showed the same level of synchrony as in healthy controls. Our findings suggest persistently high sensorimotor network synchrony, coupled with transiently (at least 1 min) low posterior network synchrony, may be a state predisposing to generalized spike-wave discharge onset. Our findings also show that EEG onset and associated MRI signal amplitude change is embedded in a considerably longer period of evolving brain network states before and after discharge events.

BOLD temporal variability differentiates wakefulness from anesthesia-induced unconsciousness.

Even though a number of findings, based on information content or information integration, are shown to define neural underpinnings characteristic of a conscious experience, the neurophysiological mechanism of consciousness is still poorly understood. Here, we investigated the brain activity and functional connectivity changes that occur in the isoflurane-anesthetized unconscious state in contrast to the awake state in rats (awake and/or anesthetized, n = 68 rats). We examined nine information measures previously shown to distinguish between conscious states: blood oxygen level-dependent (BOLD) variability, functional connectivity strength, modularity, weighted modularity, efficiency, clustering coefficient, small-worldness, and spatial and temporal Lempel-Ziv complexity measure. We also identified modular membership, seed-based network connectivity, and absolute and normalized power spectrums to assess the integrity of the BOLD functional networks between awake and anesthesia. fMRI BOLD variability and related absolute power were the only information measures significantly higher during the awake state compared with isoflurane anesthesia across animals, and with varying levels of anesthesia, after correcting for motion and respiration confounds. Thus, we conclude that, at least under the specific conditions examined here, global measures of information integration/sharing do not properly distinguish the anesthetized state from wakefulness, and heightened overall, global and local, BOLD variability is the most reliable determinant of conscious brain activity relative to isoflurane anesthesia. NEW & NOTEWORTHY Multiple metrics previously suggested to be able to distinguish between states of consciousness were compared, within and across rats in awake and isoflurane anesthesia-induced unconsciousness. All measures tested showed sensitivity to confounds, correcting for motion and for respiration changes due to anesthesia. Resting state local BOLD variability and the related absolute power were the only information measures that robustly differentiated wakefulness states. These results caution against the general applicability of global information measures in identifying levels of consciousness, thus challenging the popular concept that these measures reflect states of consciousness, and also pointing to local signal variability as a more reliable indicator of states of wakefulness.