Increased rates of invasive bacterial disease in late 2022.

Invasive bacterial disease is associated with significant morbidity and mortality. In winter 2022, there was an apparent increased rate of invasive bacterial disease compared to preceding years. Cross-site retrospective analysis of the three Children's Health Ireland (CHI) hospitals looking at children admitted between 1st October 2022-31st December 2022 (Q4) with community-acquired invasive bacterial disease, defined as an abscess in a normally sterile site in the head, neck and chest or isolation or PCR detection of Streptococcus pneumoniae, Neisseria meningitidis, Streptococcus pyogenes (Group A streptococcus) or Haemophilus influenzae from a normally sterile site. Case numbers were compared to Q4 in each of 2018-2021. Eighty-two children met the case definition in Q4 2022 vs 97 (Q4 2018-2021). In 2022, 42/82 (51%) were female, median age 3.75 years (1.5-8.25 years). Only 2 (2%) were immunosuppressed and 2 others (2%) had underlying neurodisability. Fifty (61%) were admitted on second or subsequent presentation to a healthcare setting. Fifty-six (68%) had an abscess in a sterile site. Bloodstream infection (positive blood culture or PCR: 24 (29%)) was the most common site of infection, followed by neck 22 (27%) and intracranial 12 (15%). Group A streptococcus (GAS) 27 (33%) was the most common organism isolated. Seven cases (9%) died in 2022 compared to 2 patients (2%) from 2018 to 2021 (p < 0.05). More children had Paediatric Overall Performance Category (POPC) scores > 1 in 2022 than 2018-2021 (p = 0.003).  Conclusion: Invasive bacterial diseases increased in Q4 2022 with higher morbidity and mortality than in the preceding 4 years. Group A streptococcal infection was the most significant organism in 2022. What is known: • Invasive bacterial disease is the leading cause of childhood mortality globally. • There was an increase in cases of invasive Group A streptococcus infections reported in many countries (including Ireland) during the winter of 2022/23. What is new: • Head, neck and chest abscesses increased in Q4 of 2022 compared to the previous 4 years combined. • Invasive bacterial infections in Q4 of 2022 were associated with higher rates of mortality (9%), paediatric intensive care unit (PICU) admission (24%) and requirement for surgical drainage or intervention (67%) than in the preceding years.

Proposal of Troglocephalinae n. subfam. (Monogenea: Monocotylidae) to accommodate existing and two new monocotylids from the gills of rhinopristiform shovelnose rays.

Troglocephalinae n. subfam. is proposed for Spinuris Doran, 1953, Neoheterocotyle Hargis, 1955, Anoplocotyloides Young, 1967, Troglocephalus rhinobatidis Young, 1967 (previously incertae sedis), Nonacotyle pristis Ogawa, 1991, Mehracotyle insolita Neifar, Euzet & Ben Hassine, 2002, Scuticotyle cairae n. gen. et sp., and Brancheocotyle imbricata n. gen. et sp. All members of the proposed new subfamily are gill parasites of shovelnose rays of the order Rhinopristiformes. The subfamilies Heterocotylinae Chisholm, Wheeler & Beverley-Burton, 1995, and Dasybatotreminae Bychowsky, 1957, are amended to exclude Spinuris, Nonacotyle, Neoheterocotyle, and Anoplocotyloides and Mehracotyle, respectively. Heterocotylinae includes gill parasites of members of the orders Myliobatiformes and Torpediniformes. Dasybatotreminae includes parasites of the gills and pharyngeal cavity of members of the orders Myliobatiformes and Rajiformes. A revised phylogeny of the Monocotylidae Taschenberg, 1879 is presented and discussed, based on 28S rDNA sequences, including new sequences for Myliocotyle pteromylaei Neifer, Euzet & Ben Hassine, 1999, Heterocotyle tokoloshei Vaughan & Chisholm, 2010, Neoheterocotyle robii Vaughan & Chisholm, 2010, and the two newly proposed species and genera. Additional locality records are also provided for Monocotylidae from off South Africa.

Extending the phenotype of posterior column ataxia with retinitis pigmentosa caused by variants in FLVCR1.

Posterior column ataxia with retinitis pigmentosa (PCARP) is a rare autosomal recessive condition due to variants in the Feline Leukemia Virus Subgroup C Cellular Receptor 1 (FLVCR1) gene which was first described in 1997. In this article, we describe a young female patient with a childhood diagnosis of retinitis pigmentosa and learning disability, presenting with progressive ataxia from her late teens. Examination revealed spastic lower limbs with absent reflexes, and reduced vibration and joint position sensation. Magnetic resonance imaging showed normal cerebellar volume and linear signal abnormality within the posterior columns of her spinal cord. Trio exome analysis confirmed two variants in FLVCR1. Our case extends the phenotype of PCARP to include learning disability and developmental delay, and highlights the importance of considering this rare condition in young adults or children with visual impairment and ataxia.

Cleaner fish are potential super-spreaders.

Cleaning symbiosis is critical for maintaining healthy biological communities in tropical marine ecosystems. However, potential negative impacts of mutualism, such as the transmission of pathogens and parasites during cleaning interactions, have rarely been evaluated. Here, we investigated whether the dedicated bluestreak cleaner wrasse, Labroides dimidiatus, is susceptible to and can transmit generalist ectoparasites between client fish. In laboratory experiments, L. dimidiatus were exposed to infective stages of three generalist ectoparasite species with contrasting life histories. Labroides dimidiatus were susceptible to infection by the gnathiid isopod Gnathia aureamaculosa, but were significantly less susceptible to the ciliate protozoan Cryptocaryon irritans and the monogenean flatworm Neobenedenia girellae, compared with control host species (Coris batuensis or Lates calcarifer). The potential for parasite transmission from a client fish to the cleaner fish was simulated using experimentally transplanted mobile adult (i.e. egg-producing) monogenean flatworms on L. dimidiatus. Parasites remained attached to cleaners for an average of 2 days, during which parasite egg production continued, but was reduced compared with that on control fish. Over this timespan, a wild cleaner may engage in several thousand cleaning interactions, providing numerous opportunities for mobile parasites to exploit cleaners as vectors. Our study provides the first experimental evidence that L. dimidiatus exhibits resistance to infective stages of some parasites yet has the potential to temporarily transport adult parasites. We propose that some parasites that evade being eaten by cleaner fish could exploit cleaning interactions as a mechanism for transmission and spread.

An analysis of complaints about hospital care in the Republic of Ireland.

BACKGROUND: Patients and family members make complaints about their hospital care in order to express their dissatisfaction with the care received and prompt quality improvement. Increasingly, it is being understood that these complaints could serve as important data on how to improve care if analysed using a standardized tool. The use of the Healthcare Complaints Analysis Tool (HCAT) for this purpose has emerged internationally for quality and safety improvement. Previous work has identified hot spots (areas in care where harm occurs frequently) and blind spots (areas in care that are difficult for staff members to observe) from complaints analysis. This study aimed to (i) apply the HCAT to a sample of complaints about hospital care in the Republic of Ireland (RoI) to identify hot spots and blind spots in care and (ii) compare the findings of this analysis to a previously published study on hospital complaints in the UK. METHODS: A sample of complaints was taken from 16 hospitals in the RoI in Quarter 4 of 2019 (n = 641). These complaints were coded using the HCAT to classify complaints by domain, category, severity, stage of care and harm. Chi-squared tests were used to identify hot spots, and logistic regression was used to identify blind spots. The findings of this study were compared to a previously published UK study that used HCAT to identify hot spots and blind spots. RESULTS: Hot spots were identified in Irish hospital complaints while patients were receiving care on the ward, during initial examination and diagnosis, and while they were undergoing operations or procedures. This aligned with hot spots identified in the UK study. Blind spots were found for systemic problems, where patients experience multiple issues across their care. CONCLUSIONS: Hot spots and blind spots for patient harm can be identified in hospital care using the HCAT analysis. These in turn could be used to inform improvement interventions, and direct stakeholders to areas that require urgent attention. This study also highlights the promise of the HCAT for use across different healthcare systems, with similar results emerging from the RoI and the UK.

Fixel-based Analysis of Diffusion MRI: Methods, Applications, Challenges and Opportunities.

Diffusion MRI has provided the neuroimaging community with a powerful tool to acquire in-vivo data sensitive to microstructural features of white matter, up to 3 orders of magnitude smaller than typical voxel sizes. The key to extracting such valuable information lies in complex modelling techniques, which form the link between the rich diffusion MRI data and various metrics related to the microstructural organization. Over time, increasingly advanced techniques have been developed, up to the point where some diffusion MRI models can now provide access to properties specific to individual fibre populations in each voxel in the presence of multiple "crossing" fibre pathways. While highly valuable, such fibre-specific information poses unique challenges for typical image processing pipelines and statistical analysis. In this work, we review the "Fixel-Based Analysis" (FBA) framework, which implements bespoke solutions to this end. It has recently seen a stark increase in adoption for studies of both typical (healthy) populations as well as a wide range of clinical populations. We describe the main concepts related to Fixel-Based Analyses, as well as the methods and specific steps involved in a state-of-the-art FBA pipeline, with a focus on providing researchers with practical advice on how to interpret results. We also include an overview of the scope of all current FBA studies, categorized across a broad range of neuro-scientific domains, listing key design choices and summarizing their main results and conclusions. Finally, we critically discuss several aspects and challenges involved with the FBA framework, and outline some directions and future opportunities.

New monogeneans from the bathydemersal southern African endemic catshark, Holohalaelurus regani (Gilchrist, 1922).

The catshark genus Holohalaelurus Fowler is currently represented by five species distributed off the southern and eastern parts of the African coast. Very few parasitological records exist for any of these five species, representing a significant knowledge gap. We report the first monogenean species from the bathydemersal species Holohalaelurus regani (Gilchrist): a new species of Microbothriidae Price, 1936, Leptomicrobothrium holohalaelure n. sp. from the dorsal skin surface, and a new species of Hexabothriidae Price, 1942 representing a new genus, Scyliorhinocotyle narvaezae n. gen., n. sp., from the gill lamellae. Both monogenean records represent the first for any member of the catshark genus Holohalaelurus. Previously we focused on the identification of monogenean taxa of emerging veterinary importance for public aquaria. We now begin a focused effort to document a generally unexplored monogenean biodiversity from diverse marine habitats off South Africa.

Sea lice (Copepoda: Caligidae) from South Africa, with descriptions of two new species of Caligus.

Thirteen species of sea lice (family Caligidae) are reported from a range of elasmobranch and actinopterygian fishes caught off South Africa or obtained from public aquaria in South Africa. Two new species of Caligus Müller, 1785 are described: C. linearis n. sp. from Pomatomus saltatrix (Linnaeus) and C. tumulus n. sp. from Chrysoblephus cristiceps (Valenciennes). A supplementary description is provided for both sexes of Caligus tetrodontis Barnard, 1948 taken from Amblyrhynchotes honckenii (Bloch) and previous records of this parasite from South African fishes are critically reviewed. It is concluded that Caligus material from Arothron hispidus Linnaeus was previously misidentified as C. tetrodontis and is in urgent need of re-examination. Morphological and molecular observations on Caligus furcisetifer Redkar, Rangnekar & Murti, 1949 indicate that this copepod is phenotypically and genetically identical to Lepeophtheirus natalensis Kensley & Grindley, 1973, and the latter becomes a junior subjective synonym of C. furcisetifer. We include new geographical distribution records for Caligus longipedis Bassett-Smith, 1898, C. rufimaculatus Wilson, 1905 and Lepeophtheirus spinifer Kirtisinghe, 1937, extending into South African waters, as well as both new distribution and host records for Alebion gracilis Wilson, 1905, Caligus dakari van Beneden, 1892 and Lepeophtheirus acutus Heegaard, 1943. The molecular analysis confirmed the monophyly of the genus Caligus. The South African species of Caligus did not cluster together, but the two included South African species of Lepeophtheirus were recovered as sister taxa.

Invasive non-native species likely to threaten biodiversity and ecosystems in the Antarctic Peninsula region.

The Antarctic is considered to be a pristine environment relative to other regions of the Earth, but it is increasingly vulnerable to invasions by marine, freshwater and terrestrial non-native species. The Antarctic Peninsula region (APR), which encompasses the Antarctic Peninsula, South Shetland Islands and South Orkney Islands, is by far the most invaded part of the Antarctica continent. The risk of introduction of invasive non-native species to the APR is likely to increase with predicted increases in the intensity, diversity and distribution of human activities. Parties that are signatories to the Antarctic Treaty have called for regional assessments of non-native species risk. In response, taxonomic and Antarctic experts undertook a horizon scanning exercise using expert opinion and consensus approaches to identify the species that are likely to present the highest risk to biodiversity and ecosystems within the APR over the next 10 years. One hundred and three species, currently absent in the APR, were identified as relevant for review, with 13 species identified as presenting a high risk of invading the APR. Marine invertebrates dominated the list of highest risk species, with flowering plants and terrestrial invertebrates also represented; however, vertebrate species were thought unlikely to establish in the APR within the 10 year timeframe. We recommend (a) the further development and application of biosecurity measures by all stakeholders active in the APR, including surveillance for species such as those identified during this horizon scanning exercise, and (b) use of this methodology across the other regions of Antarctica. Without the application of appropriate biosecurity measures, rates of introductions and invasions within the APR are likely to increase, resulting in negative consequences for the biodiversity of the whole continent, as introduced species establish and spread further due to climate change and increasing human activity.

Clinical benefit of presurgical EEG-fMRI in difficult-to-localize focal epilepsy: A single-institution retrospective review.

OBJECTIVE: The aim of this report is to present our clinical experience of electroencephalography-functional magnetic resonance imaging (EEG-fMRI) in localizing the epileptogenic focus, and to evaluate the clinical impact and challenges associated with the use of EEG-fMRI in pharmacoresistant focal epilepsy. METHODS: We identified EEG-fMRI studies (n = 118) in people with focal epilepsy performed at our center from 2003 to 2018. Participants were referred from our Comprehensive Epilepsy Program in an exploratory research effort to address often difficult clinical questions, due to complex and difficult-to-localize epilepsy. We assessed the success of each study, the clinical utility of the result, and when surgery was performed, the postoperative outcome. RESULTS: Overall, 50% of EEG-fMRI studies were successful, meaning that data were of good quality and interictal epileptiform discharges were recorded. With an altered recruitment strategy since 2012 with increased inclusion of patients who were inpatients for video-EEG monitoring, we found that this patients in this selected group were more likely to have epileptic discharges detected during EEG-fMRI (96% of inpatients vs 29% of outpatients, P<.0001). To date, 48% (57 of 118) of patients have undergone epilepsy surgery. In 10 cases (17% of the 59 successful studies) the EEG-fMRI result had a "critical impact" on the surgical decision. These patients were difficult to localize because of subtle abnormalities, apparently normal MRI, or extensive structural abnormalities. All 10 had a good seizure outcome at 1 year after surgery (mean follow-up 6.5 years). SIGNIFICANCE: EEG-fMRI results can assist identification of the epileptogenic focus in otherwise difficult-to-localize cases of pharmacoresistant focal epilepsy. Surgery determined largely by localization from the EEG-fMRI result can lead to good seizure outcomes. A limitation of this study is its retrospective design with nonconsecutive recruitment. Prospective clinical trials with well-defined inclusion criteria are needed to determine the overall benefit of EEG-fMRI for preoperative localization and postoperative outcome in focal epilepsy.

Ataxia pancytopenia syndrome due to SAMD9L mutation presenting as demyelinating neuropathy.

Ataxia pancytopenia (ATXPC) syndrome due to gain-of-function pathogenic variants in the SAMD9L gene has been described in 38 patients to date. It is characterized by variable neurological and hematological phenotypes including ataxia, pyramidal signs, cytopenias, and hematological malignancies. Peripheral neuropathy with slowing of conduction velocities has been reported in only two affected individuals. We describe a female with childhood onset neuropathy diagnosed as Charcot-Marie-Tooth disease type 1 with onset of cerebellar ataxia in her 50s. Cerebellar, pyramidal, and neuropathic features were found on examination. Additionally, she also had conjunctival telangiectasia. Nerve conduction studies confirmed a demyelinating neuropathy. MRI brain showed cerebellar atrophy with diffuse white matter hyperintensities. OCT demonstrated global thinning of the retinal nerve fiber layer (RNFL). Full blood count has always been normal. A previously described pathogenic variant in SAMD9L [c.2956C>T p.(Arg986Cys)] was identified on whole exome sequencing. This case extends the previously described phenotype to include conjunctival telangiectasia and RNFL thinning and suggests that ATXPC syndrome should be considered in the differential for inherited demyelinating neuropathies.

Enlarged hippocampal fissure in psychosis of epilepsy.

Psychosis of epilepsy (POE) can be a devastating condition, and its neurobiological basis remains unclear. In a previous study, we identified reduced posterior hippocampal volumes in patients with POE. The hippocampus can be further subdivided into anatomically and functionally distinct subfields that, along with the hippocampal fissure, have been shown to be selectively affected in other psychotic disorders and are not captured by gross measures of hippocampal volume. Therefore, in this study, we compared the volume of selected hippocampal subfields and the hippocampal fissure in 31 patients with POE with 31 patients with epilepsy without psychosis. Cortical reconstruction, volumetric segmentation, and calculation of hippocampal subfields and the hippocampal fissure were performed using FreeSurfer. The group with POE had larger hippocampal fissures bilaterally compared with controls with epilepsy, which was significant on the right. There were no significant differences in the volumes of the hippocampal subfields between the two groups. Our findings suggest abnormal development of the hippocampus in POE. They support and expand the neurodevelopmental model of psychosis, which holds that early life stressors lead to abnormal neurodevelopmental processes, which underpin the onset of psychosis in later life. In line with this model, the findings of the present study suggest that enlarged hippocampal fissures may be a biomarker of abnormal neurodevelopment and risk for psychosis in patients with epilepsy.

Cryopreservation of articular cartilage. Part 3: The liquidus-tracking method.

Although it is relatively straightforward to cryopreserve living isolated chondrocytes, at the present time there is no satisfactory method to preserve surgical grafts between the time of procurement or manufacture and actual use. In earlier papers we have established that the cryoprotectants dimethyl sulphoxide or propylene glycol do penetrate into this tissue very rapidly. Chondrocytes are not unusually susceptible to osmotic stress; in fact they appear to be particularly resistant. It appears that damage is associated with the formation of ice per se, even at cooling rates that are optimal for the cryopreservation of isolated chondrocytes. We then showed that current methods of cartilage cryopreservation involve the nucleation and growth of ice crystals within the chondrons rather than ice being restricted to the surrounding acellular matrix. This finding established the need to avoid the crystallization of ice-in other words, vitrification. Song and his colleagues have published a vitrification method that is based on the use of one of Fahy's vitrification formulations. We confirmed the effectiveness of this method but found it to be very dependent on ultra rapid warming. However, we were able to develop a 'liquidus-tracking' method that completely avoids the crystallization of ice and does not require rapid warming. The ability of cartilage preserved in this way to incorporate sulphate into newly synthesized glycosaminoglycans (GAGs) approached 70% of that of fresh control cartilage. In this method the rates of cooling and warming can be very low, which is essential for any method that is to be used in Tissue Banks to process the bulky grafts that are required by orthopaedic surgeons. Work is continuing to refine this method for Tissue Bank use.

Bilateral volume reduction in posterior hippocampus in psychosis of epilepsy.

OBJECTIVE: Psychosis of epilepsy (POE) occurs more frequently in temporal lobe epilepsy, raising the question as to whether abnormalities of the hippocampus are aetiologically important. Despite decades of investigation, it is unclear whether hippocampal volume is reduced in POE, perhaps due to small sample sizes and methodological limitations of past research. METHODS: In this study, we examined the volume of the total hippocampus, and the hippocampal head, body and tail, in a large cohort of patients with POE and patients with epilepsy without psychosis (EC). One hundred adults participated: 50 with POE and 50 EC. Total and subregional hippocampal volumes were manually traced and compared between (1) POE and EC; (2) POE with temporal lobe epilepsy, extratemporal lobe epilepsy and generalised epilepsy; and (3) patients with POE with postictal psychosis (PIP) and interictal psychosis (IP). RESULTS: Compared with EC the POE group had smaller total left hippocampus volume (13.5% decrease, p<0.001), and smaller left hippocampal body (13.3% decrease, p=0.002), and left (41.5% decrease, p<0.001) and right (36.4% decrease, p<0.001) hippocampal tail volumes. Hippocampal head volumes did not differ between groups. CONCLUSION: Posterior hippocampal volumes are bilaterally reduced in POE. Volume loss was observed on a posteroanterior gradient, with severe decreases in the tail and moderate volume decreases in the body, with no difference in the hippocampal head. Posterior hippocampal atrophy is evident to a similar degree in PIP and IP. Our findings converge with those reported for the paradigmatic psychotic disorder, schizophrenia, and suggest that posterior hippocampal atrophy may serve as a biomarker of the risk for psychosis, including in patients with epilepsy.

Fibre-specific white matter reductions in Alzheimer's disease and mild cognitive impairment.

Alzheimer's disease is increasingly considered a large-scale network disconnection syndrome, associated with progressive aggregation of pathological proteins, cortical atrophy, and functional disconnections between brain regions. These pathological changes are posited to arise in a stereotypical spatiotemporal manner, targeting intrinsic networks in the brain, most notably the default mode network. While this network-specific disruption has been thoroughly studied with functional neuroimaging, changes to specific white matter fibre pathways within the brain's structural networks have not been closely investigated, largely due to the challenges of modelling complex white matter structure. Here, we applied a novel technique known as 'fixel-based analysis' to comprehensively investigate fibre tract-specific differences at a within-voxel level (called 'fixels') to assess potential axonal loss in subjects with Alzheimer's disease and mild cognitive impairment. We hypothesized that patients with Alzheimer's disease would exhibit extensive degeneration across key fibre pathways connecting default network nodes, while patients with mild cognitive impairment would exhibit selective degeneration within fibre pathways connecting regions previously identified as functionally implicated early in Alzheimer's disease. Diffusion MRI data from Alzheimer's disease (n = 49), mild cognitive impairment (n = 33), and healthy elderly control subjects (n = 95) were obtained from the Australian Imaging, Biomarkers and Lifestyle study of ageing. We assessed microstructural differences in fibre density, and macrostructural differences in fibre bundle morphology using fixel-based analysis. Whole-brain analysis was performed to compare groups across all white matter fixels. Subsequently, we performed a tract of interest analysis comparing fibre density and cross-section across 11 selected white matter tracts, to investigate potentially subtle degeneration within fibre pathways in mild cognitive impairment, initially by clinical diagnosis alone, and then by including amyloid status (i.e. a positive or negative amyloid PET scan). Our whole-brain analysis revealed significant white matter loss manifesting both microstructurally and macrostructurally in Alzheimer's disease patients, evident in specific fibre pathways associated with default mode network nodes. Reductions in fibre density and cross-section in mild cognitive impairment patients were only exhibited within the posterior cingulum when statistical analyses were limited to tracts of interest. Interestingly, these degenerative changes did not appear to be associated with high amyloid accumulation, given that amyloid-negative, but not positive, mild cognitive impairment subjects exhibited subtle focal left posterior cingulum deficits. The findings of this study demonstrated a stereotypical distribution of white matter degeneration in patients with Alzheimer's disease, which was in line with canonical findings from other imaging modalities, and with a network-based conceptualization of the disease.awx355media15726254535001.

Do safety briefings improve patient safety in the acute hospital setting? A systematic review.

AIMS: To synthesize current knowledge about the impact of safety briefings as an intervention to improve patient safety. BACKGROUND: Improving safety in health care remains an ongoing challenge. There is a lack of evidence underpinning safety enhancing interventions. DESIGN: Mixed method multi-level synthesis. DATA SOURCES: Four health literature databases were searched (Cinahl, Medline, Scopus and Health Business Elite) from January 2002 - March 2017. REVIEW METHODS: Thomas and Harden approach to mixed method synthesis. RESULTS: Following quality appraisal, 12 studies were included. There was significant heterogeneity in study aims, measures, and outcomes. Findings showed that safety briefings achieved beneficial outcomes and can improve safety culture. Outcomes included improved risk identification, reduced falls, enhanced relationships, increased incident reporting, ability to voice concerns, and reduced length of stay. CONCLUSION: Healthcare leaders should embrace the potential of safety briefings by promoting their effective use whilst allowing for local adaptation.

Roles of the Clinical Ethics Consultant: A Response to Kornfeld and Prager.

We believe that clinical ethics consultants (CECs) should offer advice, options, and recommendations to attending physicians and their teams. In their article in this issue of The Journal of Clinical Ethics, however, Kornfeld and Prager give CECs a somewhat different role. The CEC they describe may at times be more aptly understood as a medical interventionist who appropriates the roles of the attending physician and the medical team than as a traditional CEC. In these remarks, we distinguish the role of the CEC from that of the physician, in contrast to some of these authors' recommendations, which confuse the two roles.

Tract-specific atrophy in focal epilepsy: Disease, genetics, or seizures?

OBJECTIVE: To investigate whether genetics, underlying pathology, or repeated seizures contribute to atrophy in specific white matter tracts. METHODS: Medically refractory unilateral temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS-TLE, n = 26) was studied as an archetype of focal epilepsy, using fixel-based analysis of diffusion-weighted imaging. A genetic effect was assessed in first-degree relatives of HS-TLE subjects who did not have epilepsy themselves (HS-1°Rel; n = 26). The role of disease process was uncovered by comparing HS-TLE to unilateral TLE with normal clinical magnetic resonance imaging (MRI-neg TLE; n = 26, matched for seizure severity). The effect of focal seizures was inferred from lateralized atrophy common to both HS-TLE and MRI-neg TLE, in comparison to healthy controls (n = 76). RESULTS: HS-1 °Rel had bilaterally small hippocampi, but no focal white matter atrophy was detected, indicating a limited effect of genetics. HS-TLE subjects had lateralized atrophy of most temporal lobe tracts, and hippocampal volumes in HS-TLE correlated with parahippocampal cingulum and anterior commissure atrophy, indicating an effect of the underlying pathology. Ipsilateral atrophy of the tapetum, uncinate, and inferior fronto-occipital fasciculus was found in both HS-TLE and MRI-neg TLE, suggesting a common lateralized effect of focal seizures. Both epilepsy groups had bilateral atrophy of the dorsal cingulum and corpus callosum fibers, which we interpret as a consequence of bilateral insults (potentially generalized seizures and/or medications). INTERPRETATION: Underlying pathology, repeated focal seizures, and global insults each contribute to atrophy in specific tracts. Genetic factors make less of a contribution in this cohort. A multifactorial model of white matter atrophy in focal epilepsy is proposed. Ann Neurol 2017;81:240-250.

A Novel Group-Fused Sparse Partial Correlation Method for Simultaneous Estimation of Functional Networks in Group Comparison Studies.

The conventional way to estimate functional networks is primarily based on Pearson correlation along with classic Fisher Z test. In general, networks are usually calculated at the individual-level and subsequently aggregated to obtain group-level networks. However, such estimated networks are inevitably affected by the inherent large inter-subject variability. A joint graphical model with Stability Selection (JGMSS) method was recently shown to effectively reduce inter-subject variability, mainly caused by confounding variations, by simultaneously estimating individual-level networks from a group. However, its benefits might be compromised when two groups are being compared, given that JGMSS is blinded to other groups when it is applied to estimate networks from a given group. We propose a novel method for robustly estimating networks from two groups by using group-fused multiple graphical-lasso combined with stability selection, named GMGLASS. Specifically, by simultaneously estimating similar within-group networks and between-group difference, it is possible to address inter-subject variability of estimated individual networks inherently related with existing methods such as Fisher Z test, and issues related to JGMSS ignoring between-group information in group comparisons. To evaluate the performance of GMGLASS in terms of a few key network metrics, as well as to compare with JGMSS and Fisher Z test, they are applied to both simulated and in vivo data. As a method aiming for group comparison studies, our study involves two groups for each case, i.e., normal control and patient groups; for in vivo data, we focus on a group of patients with right mesial temporal lobe epilepsy.

Electrical stimulation of the piriform cortex for the treatment of epilepsy: A review of the supporting evidence.

In this review, we consider how the piriform cortex is engaged in both focal and generalized epilepsy networks and postulate the various neural pathways that can be effectively neuromodulated by stimulation at this site. This highlights the common involvement of the piriform cortex in epilepsy. We address both current and future preclinical studies of deep brain stimulation (DBS) of the piriform cortex, with attention to the critical features of these trials that will enable them to be of greatest utility in informing clinical translation. Although recent DBS trials have utilized thalamic targets, electrical stimulation of the piriform cortex may also be a useful intervention for people with epilepsy. However, more work is required to develop a solid foundation for this approach before considering human trials.