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The little brown bat (Myotis lucifugus) is an endangered species that occurs throughout most of North America. The recovery strategy for little brown bats in Canada identifies a need to understand habitat use and protect important bat habitat across the species' Canadian range; however, bat roosting habitat requirements have not been well studied in mountainous environments within the northern part of the species' range. Our objective was to understand the use of building and natural roosts by female little brown bats in the Canadian Rocky Mountains. Over two summers, we captured little brown bats in Banff, Yoho, and Kootenay National Parks, in Alberta and British Columbia, Canada, and tracked 49 females to their day roosts. Buildings were the only roost type used by radio‐tagged bats of all reproductive stages, the dominant roost type used throughout the reproductive period, and the only structures in which we located maternity colonies. Buildings also appeared to shape the distribution of foraging female and reproductive female bats such that few were captured at long distances from towns and building clusters. Compared with bats in more southern and in non‐mountainous areas, bats in our study area had delayed juvenile weaning and volancy, began hibernation early, and had low reproductive rates. We suggest that buildings are a key habitat for female little brown bats to persist at their current levels in our study area, by providing thermal conditions that promote overwinter survival; additional reproductive delays caused by torpor use in cool natural roosts would likely reduce juvenile and adult female overwinter survival below the levels required to sustain populations. Nevertheless, building colonies were unusually small, and bats had relatively low fidelity to particular building roosts, suggesting that building roosts may not consistently meet bats' needs. Some nonreproductive and pregnant females also frequently used natural roosts, particularly after colder nights; these roosts may be important in facilitating torpor and energy conservation for these bats. Because bats are long‐lived with low reproductive output and low juvenile survival, addressing the needs of both reproductive and nonreproductive individuals is important for population persistence. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to describe the clinical features of contactin-associated protein-like 2 (CASPR2)-IgG-associated seizures., Methods: Nine patients were retrospectively collected from two epilepsy centers. For each patient we obtained a full clinical, neurophysiological, and MRI study along with detection of antineuronal autoantibodies from serum and CSF. The patients were followed up for 1-6 years., Results: The patients were nine male subjects aged 56-85 years (mean: 66) with a 1- to 14-year (mean: 6,3 median: 6) history of seizures. The seizures were classified as focal onset seizures with impaired awareness, usually preceded by epigastric aura (two), piloerection (two), olfactory hallucinations (two), nausea and dizziness (one). Tonic-clonic seizures were present in five patients. Seizure frequency was high in six cases and sporadic in three. Most patients reported memory impairment (eight) or behavioral/mood changes (four). Interictal EEGs usually showed bilateral or unilateral temporal epileptiform abnormalities. A number of seizures arising from the temporal lobes, with bilateral asynchronous onset, were recorded on long-term video-EEG monitoring in two patients. MRI disclosed nonspecific white matter T2 hyperintensities suggestive of chronic vascular changes in four patients and bilateral T2-FLAIR amygdalo-hippocampal hyperintensity in three cases. Neuropsychological study demonstrated various degrees of cognitive impairment in the majority of cases. Increased titers of CASPR2 autoantibodies were detected in the serum and CSF, which persisted over time in four cases. Drug resistance to common anti-seizure medications was present in seven cases who benefited from immunotherapy., Significance: CASPR2-IgG testing should be performed among old male patients with a recent or even not recent onset of focal seizures with impaired awareness particularly when these seizures are accompanied by cognitive impairment or behavioral disturbances. In these cases, anti-seizure medications may be ineffective while immunotherapy may lead to a prompt improvement of seizures and cognitive deficits., (© 2024 International League Against Epilepsy.)

Objective: Cenobamate (CNB), a recently approved antiseizure medication by the European Medicines Agency (EMA), serves as an adjunctive therapy for focal-onset seizures in adult patients unresponsive to at least two other treatments. Administered in polytherapy, CNB can potentially interact with co-administered drugs in epilepsy patients, necessitating dose adjustments and the need for effective therapeutic drug monitoring (TDM)., Methods: In this study, we introduce a novel LC-MS/MS method for precise CNB quantification using Volumetric Absorptive Microsampling (VAMS), following validation according to ICH guidelines M10. VAMS samples are efficiently extracted with 200 μL of methanol, with chromatographic separation achieved using an Acquity UPLC HSS PFP column. The method's efficacy was confirmed through its application to real samples from adult CNB-treated patients., Results: Our results demonstrate that the method exhibits linearity within the range of 0.05-30 mg/L, with intra- and inter-run precision ranging from 1% to 8% and accuracy from 1% to 10% based on 30 μL of sample. Furthermore, CNB stability in VAMS is confirmed for up to 15 days at 25°C and -20°C. Importantly, no significant difference was observed between CNB concentrations in VAMS samples and those in plasma obtained from venous blood., Significance: This VAMS-based LC-MS/MS method presents a robust alternative for TDM in CNB-treated patients. Future investigations should explore CNB concentrations in capillary blood and assess their correlation with plasma levels to further enhance its clinical utility., Plain Language Summary: Cenobamate is an antiepileptic drug and used for treatment of focal-onset seizures in adult patients (≥18 age). TDM can prevent drug interactions and minimize drug toxicity. The aim of this work is to evaluate volumetric absorptive microsampling (VAMS) from capillary blood as an alternative strategy for TDM in patients treated with the newly antiepileptic drug. Our method is suitable for TDM, and this study suggests that VAMS allows monitoring of cenobamate concentration and can offer valuable support for personalized therapy in refractory epilepsy., (© 2024 The Authors. Epilepsia Open published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Transition from the paediatric holistic approach to the adult more individual care of epilepsy is a process that carries a high level of complexity and involves many actors. It is a mandatory step so to provide a gold-standard quality of care in young people with epilepsy. Its failure is strongly associated with a poor epilepsy, cognitive, and behavioural outcome. Although the interest of the scientific community on transition has increased, in the clinical practice it is still considered a sensitive issue, in particular for adult neurologists. In this study we aimed at exploring pitfalls and unmet needs of transition from the adult neurologists' perspective. A short survey, aimed to adult neurologists, was designed to explore i) whether transition is considered a problematic issue for the adult neurologist, ii) how transition impact his/her clinical practice, iii) which are the major problems related to the process, and iv) how transition may be improved. The results of the survey showed that transition is felt as a complex process that needs a shared action plan between child and adult neurologists, possibly with multidisciplinary team meetings as well as a higher training on childhood epilepsies for the adult neurologist., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Epileptic seizures are frequently associated with liver dysfunction and alcoholism. Subacute encephalopathy with seizures in chronic alcoholics (SESA) is an underrecognized condition with peculiar clinical, EEG and neuroradiological features.We report the case of a 58-year-old man with previous alcohol use disorder (AUD) and acute-on chronic liver failure on alcohol-related cirrhosis, referred for urgent Orthotopic Liver Transplantation evaluation. The patient presented with delirium, aphasia and progressive deterioration of consciousness leading to intensive care unit admission. EEG showed slow activity with superimposed lateralized periodic discharges (LPDs) over the left temporo-occipital regions and ictal discharges with focal motor phenomena, consistent with focal status epilepticus. Antiseizure treatment with lacosamide and levetiracetam was administered with progressive improvement of consciousness.Brain MRI disclosed T2/FLAIR areas of hyperintensity in the left pulvinar and T2/FLAIR hyperintensity with corresponding DWI hyperintensity in the left hippocampal cortex, suggestive of post/peri-ictal excitotoxic changes with anatomical correspondence to focal LPDs distribution. SWI demonstrated decreased prominence of cortical veins in the left temporo-occipital region consistent with increased venous blood oxygenation in compensatory hyperperfusion.In conclusion, SESA should be suspected in the differential diagnosis of patients with AUD presenting with focal neurological deficits, seizures and focal EEG abnormalities. In this context, EEG and brain MRI represent useful tools with both diagnostic and prognostic value., (© 2024. Fondazione Società Italiana di Neurologia.)

Objectives: DEPDC5 -related epilepsy carries an increased risk of sudden unexpected death in epilepsy. We evaluated the occurrence and features of ictal central apnea (ICA) in patients with pathogenic sequence variant in DEPDC5 ., Methods: We reviewed data of 108 patients collected in 2 independent cohorts of patients with focal epilepsy who prospectively underwent long-term video-EEG monitoring (LTVM) with cardiorespiratory polygraphy. All patients underwent (1) at least an overnight polysomnography, (2) a high-field (3T) brain MRI study, and (3) CSF analysis when clinically indicated. Genetic testing (next-generation sequencing [NGS]) was offered for diagnostic purposes to patients with focal epilepsy of unknown etiology., Results: In this cohort, NGS was finally performed in 29 patients, resulting in DEPDC5 pathogenic mutations in 5 patients. According to the presence of ictal apnea events, 5 of 14 patients with ICA showed pathogenic DEPDC5 variants (35%) while none of the 15 patients without ICA showed pathogenic mutation. Notably, DEPDC5 patients showed ICA in all recorded seizures (n = 15) with apnea duration ranging from 20 seconds to more than 1 minute. All seizures were characterized by motor arrest without overt automatic behaviors during ictal apnea. Scalp EEG showed the involvement of temporal lobe leads in all events. Severe oxygen desaturation was observed in 2 cases., Discussion: In our cohort, ictal central apnea was a common finding in DEPDC5 . These results support (1) the need for respiratory polygraphy during LTVM in DEPDC5 -related epilepsy and (2) the potential relevance of genetic testing in patients with focal epilepsy of unknown etiology and ictal apnea., Competing Interests: S. Meletti received research grant support from the Ministry of Health (MOH); has received personal compensation as scientific advisory board member for UCB, Jazz pharmaceuticals, and EISAI. A.E. Vaudano has received speaker's or consultancy fees from Angelini. M. Burani, G. Giovannini, M. Pugnaghi, E. Micalizzi report no disclosures. P. Bonanni has received speaker's or consultancy fees from Angelini, EISAI, Livanova. G.M. Duma, A. Danieli, E. Osanni, F. Mambretti report no disclosures. Go to Neurology.org/NG for full disclosures., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: Ictal central apnea (ICA) is a frequent correlate of focal seizures, particularly in temporal lobe epilepsy (TLE), and regarded as a potential electroclinical biomarker of sudden unexpected death in epilepsy (SUDEP). Aims of this study are to investigate morphometric changes of subcortical structures in ICA patients and to find neuroimaging biomarkers of ICA in patients with focal epilepsy., Methods: We prospectively recruited focal epilepsy patients with recorded seizures during a video-EEG long-term monitoring with cardiorespiratory polygraphic recordings from April 2020 to September 2022. Participants were accordingly subdivided into two groups: patients with focal seizures with ICA (ICA) and without (noICA). A pool of 30 controls matched by age and sex was collected. All the participants underwent MRI scans with volumetric high-resolution T1-weighted images. Post-processing analyses included a whole-brain VBM analysis and segmentation algorithms performed with FreeSurfer., Results: Forty-six patients were recruited (aged 15-60 years): 16 ICA and 30 noICA. The whole-brain VBM analysis showed an increased gray matter volume of the amygdala ipsilateral to the epileptogenic zone (EZ) in the ICA group compared to the noICA patients. Amygdala sub-segmentation analysis revealed an increased volume of the whole amygdala, ipsilateral to the EZ compared to controls [F(1, 76) = 5.383, pFDR = 0.042] and to noICA patients ([F(1, 76) = 5.383, pFDR = 0.038], specifically of the basolateral complex (respectively F(1, 76) = 6.160, pFDR = 0.037; F(1, 76) = 5.121, pFDR = 0.034)., Interpretation: Our findings, while confirming the key role of the amygdala in participating in ictal respiratory modifications, suggest that structural modifications of the amygdala and its subnuclei may be valuable morphological biomarkers of ICA., (© 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Objective: assess the effectiveness of a new method for classifying EEG recording features through the use of tags within reports. We present feature prevalence in a sample of patients with toxic-metabolic encephalopathy and discuss the advantages of this approach over existing classification systems., Methods: during EEG report creation, tags reflecting background activity, epileptiform features and periodic discharges were selected according to the findings of each recording. Reports including the tags have been collected and processed by the EEG report parser script written in PHP language. The resulting spreadsheet was analysed to calculate the prevalence and type of EEG features in a sample group of patients with toxic-metabolic encephalopathy., Results: tag checking and extraction were very little time-consuming processes. Considering 5784 EEG recordings performed either in inpatients or outpatients over 2 years, toxic-metabolic aetiology was tagged in 218 (3.8 %). The most frequent background feature was severe slowing (5-6 Hz frequency), occurring in 79 (36.2 %). Epileptiform abnormalities were rare, reaching a maximum of 10 (4.6 %). Triphasic waves were tagged in 43 (19.7 %) recordings., Conclusions: tagging and parsing processes are very fast and integrated into the daily routine. Sample analysis in patients with toxic-metabolic encephalopathies showed EEG slowing as the prevalent feature, while triphasic waves occurred in a minority of recordings. Existing software such as "SCORE" (Holberg EEG) requires the replacement of the currently used software for EEG reporting, minimizing additional costs and training. EEG Report Parser is free and open-source software, so it can be freely adopted, modified and redistributed, allowing further improvement and adaptability., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Cognitive disruption is a debilitating comorbidity in Temporal Lobe Epilepsy (TLE). Despite recent advances, the amygdala is often neglected in studies that explore cognition in TLE. Amygdala subnuclei are differently engaged in TLE with hippocampal sclerosis (TLE-HS) compared to non-lesional TLE (TLE-MRIneg), with predominant atrophy in the first and increased volume in the latter. Herein, we aim to explore the relationship between the volumes of the amygdala and its substructures with respect to cognitive performances in a population of left-lateralized TLE with and without HS. Twenty-nine TLEs were recruited (14 TLE-HS; 15 TLE-MRIneg). After investigating the differences in the subcortical amygdalae and hippocampal volumes compared to a matched healthy control population, we explored the associations between the subnuclei of the amygdala and the hippocampal subfields with the cognitive scores in TLE patients, according to their etiology. In TLE-HS, a reduced volume of the basolateral and cortical amygdala complexes joined with whole hippocampal atrophy, was related to poorer scores in verbal memory tasks, while in TLE-MRIneg, poorer performances in attention and processing speed tasks were associated with a generalized amygdala enlargement, particularly of the basolateral and central complexes. The present findings extend our knowledge of amygdala involvement in cognition and suggest structural amygdala abnormalities as useful disease biomarkers in TLE., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S. Meletti received research grant support from the Ministry of Health (MOH), the non-profit organization Foundation “Fondazione Cassa di Risparmio di Modena - FCRM”; he has received personal compensation as scientific advisory board member for UCB and EISAI. A.E. Vaudano received personal compensation as scientific advisory board member for Angelini Pharma. None of the authors has any conflict of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To evaluate in a real clinical scenario the impact of the ILAE-recommended "Harmonized neuroimaging of epilepsy structural sequences"- HARNESS protocol in patients affected by focal epilepsy., Methods: We prospectively enrolled focal epilepsy patients who underwent a structural brain MRI between 2020 and 2021 at Modena University Hospital. For all patients, MRIs were: (a) acquired according to the HARNESS-MRI protocol (H-MRI); (b) reviewed by the same neuroradiology team. MRI outcomes measures were: the number of positive (diagnostic) and negative MRI; the type of radiological diagnosis classified in: (1) Hippocampal Sclerosis; (2) Malformations of cortical development (MCD); (3) Vascular malformations; (4) Glial scars; (5) Low-grade epilepsy-associated tumors; (6) Dual pathology. For each patient we verified for previous MRI (without HARNESS protocol, noH-MRI) and the presence of clinical information in the MRI request form. Then the measured outcomes were reviewed and compared as appropriate., Results: A total of 131 patients with H-MRI were included in the study. 100 patients out from this cohort had at least one previous noH-MRI scan. Of those, 92/100 were acquired at the same Hospital than H-MRI and 71/92 on a 3T scanner. The HARNESS protocol revealed 81 (62%) positive and 50 (38%) negative MRI, and MCD was the most common diagnosis (60%). Among the entire pool of 100 noH-MRI, 36 resulted positive with a significant difference (p < .001) compared to H-MRI. Similar findings were observed when accounting for the expert radiologists (H-MRI = 57 positive; noH-MRI = 33, p < .001) and the scanner field strength (H-MRI 43 = positive, noH-MRI = 23, p < .001), while clinical information were more present in H-MRI (p < .002)., Significance: The adoption of a standardized and optimized MRI acquisition protocol together with adequate clinical information contribute to identify a higher number of potentially epileptogenic lesions (especially FCD) thus impacting concretely on the clinical management of patients with focal epilepsy., (© 2023 The Authors. Epileptic Disorders published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background and Purpose: Ictal respiratory disturbances have increasingly been reported, in both generalized and focal seizures, especially involving the temporal lobe. Recognition of ictal breathing impairment has gained importance for the risk of sudden unexpected death in epilepsy (SUDEP). The aim of this study was to evaluate the incidence of ictal apnea (IA) and related hypoxemia during seizures., Methods: We collected and analyzed electroclinical data from consecutive patients undergoing long-term video-electroencephalographic (video-EEG) monitoring with cardiorespiratory polygraphy. Patients were recruited at the epilepsy monitoring unit of the Civil Hospital of Baggiovara, Modena Academic Hospital, from April 2020 to February 2022., Results: A total of 552 seizures were recorded in 63 patients. IA was observed in 57 of 552 (10.3%) seizures in 16 of 63 (25.4%) patients. Thirteen (81.2%) patients had focal seizures, and 11 of 16 patients showing IA had a diagnosis of temporal lobe epilepsy; two had a diagnosis of frontal lobe epilepsy and three of epileptic encephalopathy. Apnea agnosia was reported in all seizure types. Hypoxemia was observed in 25 of 57 (43.9%) seizures with IA, and the severity of hypoxemia was related to apnea duration. Apnea duration was significantly associated with epilepsy of unknown etiology (magnetic resonance imaging negative) and with older age at epilepsy onset (p &lt; 0.001)., Conclusions: Ictal respiratory changes are a frequent clinical phenomenon, more likely to occur in focal epilepsies, although detected even in patients with epileptic encephalopathy. Our findings emphasize the need for respiratory polygraphy during long-term video-EEG monitoring for diagnostic and prognostic purposes, as well as in relation to the potential link of ictal apnea with the SUDEP risk., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Together with hippocampus, the amygdala is important in the epileptogenic network of patients with temporal lobe epilepsy. Recently, an increase in amygdala volumes (i.e. amygdala enlargement) has been proposed as morphological biomarker of a subtype of temporal lobe epilepsy patients without MRI abnormalities, although other data suggest that this finding might be unspecific and not exclusive to temporal lobe epilepsy. In these studies, the amygdala is treated as a single entity, while instead it is composed of different nuclei, each with peculiar function and connection. By adopting a recently developed methodology of amygdala's subnuclei parcellation based of high-resolution T 1 -weighted image, this study aims to map specific amygdalar subnuclei participation in temporal lobe epilepsy due to hippocampal sclerosis ( n  = 24) and non-lesional temporal lobe epilepsy ( n  = 24) with respect to patients with focal extratemporal lobe epilepsies ( n  = 20) and healthy controls ( n  = 30). The volumes of amygdala subnuclei were compared between groups adopting multivariate analyses of covariance and correlated with clinical variables. Additionally, a logistic regression analysis on the nuclei resulting statistically different across groups was performed. Compared with other populations, temporal lobe epilepsy with hippocampal sclerosis showed a significant atrophy of the whole amygdala ( p Bonferroni  = 0.040), particularly the basolateral complex ( p Bonferroni  = 0.033), while the non-lesional temporal lobe epilepsy group demonstrated an isolated hypertrophy of the medial nucleus ( p Bonferroni  = 0.012). In both scenarios, the involved amygdala was ipsilateral to the epileptic focus. The medial nucleus demonstrated a volume increase even in extratemporal lobe epilepsies although contralateral to the seizure onset hemisphere ( p Bonferroni  = 0.037). Non-lesional patients with psychiatric comorbidities showed a larger ipsilateral lateral nucleus compared with those without psychiatric disorders. This exploratory study corroborates the involvement of the amygdala in temporal lobe epilepsy, particularly in mesial temporal lobe epilepsy and suggests a different amygdala subnuclei engagement depending on the aetiology and lateralization of epilepsy. Furthermore, the logistic regression analysis indicated that the basolateral complex and the medial nucleus of amygdala can be helpful to differentiate temporal lobe epilepsy with hippocampal sclerosis and with MRI negative, respectively, versus controls with a consequent potential clinical yield. Finally, the present results contribute to the literature about the amygdala enlargement in temporal lobe epilepsy, suggesting that the increased volume of amygdala can be regarded as epilepsy-related structural changes common across different syndromes whose meaning should be clarified., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

The aim of this study was to describe the electroclinical and prognostic characteristics, and to investigate the role of leukoaraiosis in outpatients with new-onset elderly focal epilepsy aged ≥60 years, referred to a tertiary epilepsy center between 2005 and December 31, 2020. Among the 720 patients who were referred to the center, we retrospectively selected 162 consecutive outpatients, with a first referral for recent-onset focal epilepsy of unknown cause (UC) or structural cause (SC), and collected a clinical and standard-Electroencephalogram (S-EEG), 24-h ambulatory EEG (A-EEG), and neuroimaging data. We also analyzed the seizure prognosis after titration of the first antiseizure medication (ASM). One hundred and four UC and 58 SC patients, followed up for 5.8 ± 5.3 years (mean ± SD), were included. Compared with the SC group, the patients with UC showed a predominance of focal seizures with impaired awareness (51.9% of cases) and focal to bilateral tonic-clonic seizures during sleep (25%); conversely, the SC group, more frequently, had focal to bilateral tonic-clonic seizures during wakefulness (39.6%) and focal aware seizures (25.8%) ( p < 0.0001). Oral or gestural automatisms were prevalent in UC epilepsy (20.2 vs. 6.9% in the SC group, p = 0.04). In UC compared to patients with SC, interictal epileptiform discharges showed a preferential temporal lobe localization ( p = 0.0007), low expression on S-EEG, and marked activation during deep Non-Rapid Eye Movement (NREM) sleep ( p = 0.003). An overall good treatment response was found in the whole sample, with a probability of seizure freedom of 68.9% for 1 year. The cumulative probability of seizure freedom was significantly higher in the UC compared with the SC group ( p < 0.0001). The prognosis was worsened by leukoaraiosis ( p = 0.012). In the late-onset focal epilepsy of unknown cause, electroclinical findings suggest a temporal lobe origin of the seizures. This group showed a better prognosis compared with the patients with structural epilepsy. Leukoaraiosis, per se , negatively impacted on seizure prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tartara, Micalizzi, Scanziani, Ballante, Paoletti and Galimberti.)

Ictal respiratory changes have been mainly described following generalized tonic-clonic seizures and recently considered to be a biomarker to assess the risk of sudden unexplained death in epilepsy (SUDEP). Nonetheless, modification of respiratory pattern can be related also to focal seizures, especially arising from the temporal lobe. Changes in cardiac function such as tachycardia or bradycardia could be often associated. We report a short case series of four patients with temporal lobe epilepsy admitted to our Epilepsy Monitoring Unit (EMU) presenting with an ictal central apnea as the first clinical manifestation of their seizures. None of these patients was aware of the occurrence of respiratory arrest. Age at onset ranged from 15 to 29 years. One patient had seizures with prolonged central apnea accompanied by a significant decrease in oxygen saturation. Neuroimaging in two patients showed alterations of mesial temporal lobe structures, including the amygdala. Recent neurophysiological studies supported the existence of a cortical network involving the limbic system that modulates downstream brainstem respiratory centers. Monitoring for respiratory changes and oxygen saturation in focal seizures is warranted for their potential value in identifying the epileptogenic zone and for a better understanding of ictal respiratory changes that could potentially define a subgroup of patients with high risk of seizure-related autonomic changes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Micalizzi, Vaudano, Giovannini, Turchi, Giunta and Meletti.)

Background: Postoperative outcomes of a third-generation porcine bioprosthesis for mitral valve replacement (MVR) have been poorly addressed. The objective of this study was to perform an independent, retrospective, multicenter study on outcomes of patients undergoing MVR with a Mosaic (Medtronic Inc, Minneapolis, MN) porcine bioprosthesis., Methods: From 1998 to 2011, 805 patients underwent MVR with a Mosaic porcine valve in 11 cardiac centers. There were 465 female patients (58%), and the overall mean age was 73.5 ± 7 years. Associated procedures included coronary artery bypass grafting (201 patients; 24.9%), aortic valve replacement (152 patients; 18.9%), tricuspid annuloplasty (187 patients; 22.3%), and other cardiac procedures (116 patients; 14.4%)., Results: Median follow-up was 44 months (interquartile range, 16 to 63), with a cumulative duration of 2.769 patient-years. Early mortality for isolated elective MVR was 3.8% (12 of 313), and overall early mortality was 7.8% (n = 63). The rate of late mortality was 3.4%/patient-year (95 late deaths). At 10 years, overall survival was 57.4% (95% confidence interval [CI], 48.8% to 67.5%), and cumulative rates of cardiac- and valve-related death were 7.4% (95% CI, 4.8% to 10.1%) and 1.1% (95% CI, 0.2% to 1.9%), respectively. The 10-year cumulative rates of thromboembolic and hemorrhagic events were 6.6% (95% CI, 1.4% to 11.8%) and 3.9% (95% CI, 0.1% to 8%), respectively, and the 10-year cumulative incidence of prosthetic valve endocarditis was 3% (95% CI, 1.2% to 4.9%). Finally, the 10-year cumulative incidences of structural valve degeneration and reoperations were 5.8% (95% CI, 0.2% to 11.5%) and 4.8% (95% CI, 0.7% to 10.3%), respectively., Conclusions: This independent, multicenter, retrospective study indicated that the Mosaic porcine bioprosthesis for MVR provides satisfactory results in terms of both early and long-term outcomes up to 14 years from its implantation., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

We describe the case of a 62-year-old man who needed a 3-vessel coronary artery bypass reoperation and mitral valve replacement. The patient's existing free left internal mammary artery graft was not functioning because of a critical stenosis in the native vessel just after the distal anastomosis. The free graft itself was in perfect condition, and we decided to reuse it. Because the course of the graft was so tortuous, we concluded that skeletonization would yield the extra length needed for reimplantation. After reimplanting the graft, we performed venous grafting and mitral valve replacement. The patient was well and had no signs of ischemia at 29 months postoperatively. There have been few reports on recycling internal mammary artery grafts in repeat coronary artery bypass grafting. To our knowledge, ours is the first report of the reimplantation of a free internal mammary artery graft on the same vessel. We describe the procedure and our decision-making process.

Background: We assess the effectiveness of thoracic endovascular aortic repair (TEVAR) in patients with thoracic artery aneurysm with a retrospective analysis of our experience and a review of the literature., Methods: Between January 2005 and December 2011, 53 patients with thoracic aortic aneurysm underwent TEVAR. We evaluated the technical success, periprocedural and long-term mortality and morbidity, and follow-up by enhanced computed tomographic scans at 1, 6, and 12 months and annually thereafter., Results: TEVAR was performed in good general conditions in 62.3% of cases and in emergency conditions in 37.7% of cases. A total of 85 endoprostheses were correctly placed, with technical success of 100%. In 18.8% of cases, a carotid-subclavian bypass was performed; 35.8% of cases required drainage of cerebrospinal fluid. Postoperative mortality was 7.5%, and in all cases patients were treated in emergency regimen. The incidence of major postoperative complications was 9.4%, with 2 cases of paraplegia. At a mean follow-up of 25.6 months, 12 cases (22.6%) of endoleak were observed: 5 cases of type IB endoleak were treated with prosthetic extensions; 7 cases of type II endoleak were not treated. There were no thrombotic occlusions, stent migrations, or fractures., Conclusion: TEVAR represents an effective option in the treatment of thoracic aortic aneurysms, with good immediate and long-term results., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: The endocannabinoid system reportedly plays a role in the pathogenesis of cardiovascular diseases. This system is expressed also in adipose tissue, which could thus be involved in cardiac disorders through modulation of metabolically triggered inflammation. The current study aims to determine the relevance of the endocannabinoid system in epicardial adipose tissue in heart disease., Methods: Expression of the endocannabinoid receptors CB1 and CB2, and of the endocannabinoid-degrading enzyme, fatty acid amidohydrolase, and activation of protein kinase A (PKA), phospholipase C (PLC), protein kinase C (PKC), endothelial nitric oxide synthase (eNOS) and inducible (i)NOS, and extracellular signal-regulated kinases 1 and 2 (ERK1/2) (a member of the reperfusion-injury salvage kinase pathway), were analyzed by Western blot in patients after coronary artery bypass surgery (ischemics; N = 18) or valve surgery (nonischemics; N = 15) and in preadipocytes isolated from epicardial adipose tissue., Results: In ischemics, the CB1-to-CB2 expression ratio shifted toward CB1 and was accompanied by higher PKA activation. In contrast, in nonischemics, CB2, fatty acid amidohydrolase, PLC and PKC, and ERK1/2 were upregulated. Moreover, NO production and iNOS-to-eNOS ratios were higher in preadipocytes from ischemics., Conclusions: These results show a different modulation and functioning of the endocannabinoid system in ischemics compared with nonischemics. Hence, while CB2, PLC and PKC, ERK1/2, and eNOS are more strongly expressed in patients without ischemic heart disease, high CB1 and PKA expression is associated with low survival intracellular pathway activation and high iNOS activation in ischemic heart disease patients. The changes in the endocannabinoid system in ischemics may contribute to cardiac dysfunction and therefore represents a potential therapeutic target., (Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

The pathophysiological relationship between coronary atherosclerosis and coronary microvessels remains undefined and the specific causative role of oxidatively modified low density lipoprotein (oxLDL) in human atherosclerosis is debated. The purposes of this study are to investigate whether coronary microvessels are involved in coronary atherosclerosis and whether increased myocardial oxLDL amount can be associated with coronary microvessel inflammation. A combination of immunohistochemical, RT-PCR and real-time PCR studies performed on myocardial biopsy specimens from patients with mitral stenosis (control hearts, CHs) and from unstable and stable angina patients (UAP and SAP), demonstrated that myocardial oxLDL was associated with a chronic low-grade inflammation in SAP and with a severe high grade inflammation in UAP. oxLDL amount was notably higher in UAP than in SAP and in UAP the high grade of inflammation was correlated with the increased amount of oxLDL in endothelial cells and macrophages. The exaggerated amount of oxLDL in UAP and the interaction of oxLDL with lectin-like oxLDL (LOX-1) receptor are amplified by the activation of transcriptional factor octamere 1 (OCT-1) with consequent activation of a series of inflammatory endothelial feed-back mechanisms resulting in LOX-1 gene over-expression, endothelial inflammation as well as uncontrolled nuclear factor kappa B (NFkB) activation. Moreover, in UAP genes for signal transducer and activator transcriptional factor 1α (STAT1α), angiotensin converting enzyme (ACE) and numerous pro-inflammatory cytokines were over-expressed. The present results may have clinical relevance because they show that coronary atherosclerosis is a disease not confined to the large arteries but involving the whole coronary tree. In UAP the exaggerated amount of myocardial oxLDL is associated with widespread high grade microvessel inflammation., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: It is uncertain whether mitral valve replacement is really inferior to mitral valve repair for the treatment of chronic ischemic mitral regurgitation. This multicenter study aimed at providing a contribution to this issue., Methods: Of 1006 patients with chronic ischemic mitral regurgitation and impaired left ventricular function (ejection fraction < 40%) operated on at 13 Italian institutions between 1996 and 2011, 298 (29.6%) underwent mitral valve replacement whereas 708 (70.4%) received mitral valve repair. Propensity scores were calculated by a nonparsimonious multivariable logistic regression, and 244 pairs of patients were matched successfully using calipers of width 0.2 standard deviation of the logit of the propensity scores. The postmatching median standardized difference was 0.024 (range, 0-0.037) and in none of the covariates did it exceed 10%., Results: Early deaths were 3.3% (n = 8) in mitral valve repair versus 5.3% (n = 13) in mitral valve replacement (P = .32). Eight-year survival was 81.6% ± 2.8% and 79.6% ± 4.8% (P = .42), respectively. Actual freedom from all-cause reoperation and valve-related reoperation were 64.3% ± 4.3% versus 80% ± 4.1%, and 71.3% ± 3.5% versus 85.5% ± 3.9 in mitral valve repair and mitral valve replacement, respectively (P < .001). Actual freedom from all valve-related complications was 68.3% ± 3.1% versus 69.9% ± 3.3% in mitral valve repair and mitral valve replacement, respectively (P = .78). Left ventricular function did not improved significantly, and it was comparable in the 2 groups postoperatively (36.9% vs 38.5%, P = .66). At competing regression analysis, mitral valve repair was a strong predictor of reoperation (hazard ratio, 2.84; P < .001)., Conclusions: Mitral valve replacement is a suitable option for patients with chronic ischemic mitral regurgitation and impaired left ventricular function. It provides better results in terms of freedom from reoperation with comparable valve-related complication rates., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Bronchial artery aneurysm (BAA) represents a rare, but dangerous, pathology because its rupture can cause a life-threatening hemorrhage; opportune treatment is mandatory when a definite diagnosis is obtained. There are several reports of endovascular treatment of BAA with transcatheter arterial embolization and only few cases treated with aortic stent-graft exclusion. We report a case of mediastinal BAA close to thoracic aorta treated with a combined approach of stent-graft occlusion of the inflow and coil embolization of the outflow arteries., (Copyright © 2012 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.)

Acute cardiac failure caused by myocardial infarction or inadequate cardioprotection during heart surgery is associated with increased mortality and morbidity. Levosimendan is a new drug used in heart failure though it is limited by the systemic hypotension, which develops with intravenous administration. Intracoronary (IC) administration however should affect systemic circulation less while maintaining the beneficial cardiac effects of the drug. We herewith report the results from the first such clinical series. Levosimendan was administered IC in 33 consecutive patients who developed cardiogenic shock during heart surgery and were unable to wean off cardiopulmonary bypass despite maximal support. Preadministration/postadministration coronary graft flows, hemodynamic parameters, left ventricular function, and metabolic requirements were measured and compared. Levosimendan significantly increased graft flows and improved hemodynamic parameters. Systolic blood pressure (93 ± 26.4 vs. 106 ± 18.2 mm Hg, P < 0.05) and cardiac index (2.0 ± 0.5 vs. 3.1 ± 0.2, P < 0.001) were increased, whereas systemic vascular resistance (1470.7 ± 114 vs. 1195.8 ± 112, P < 0.01) was reduced. Better myocardial perfusion improved metabolic requirements, with myocardial oxygen extraction and glucose uptake increasing by 72% and 74%, respectively, whereas lactate production was reduced by 64%. Echocardiography demonstrated additional ventricular segment recruitment. Therefore, IC Levosimendan administration in acute heart failure is safe and efficacious producing improved cardiac function without significant detrimental hypotension.

Objective: Levosimendan has been reported to exert cardioprotection. In this study, we have examined the cardiac effects of different doses of intracoronary levosimendan on ischemia/reperfusion injuries, and the involvement of K(ATP) channels and nitric oxide (NO)., Methods: The experiments were performed in a total of 56 anesthetized pigs. In 21 pigs, 1.5, 5 and 12 μg min(-1) levosimendan was infused over 15 min into the coronary artery at the onset of 1 h reperfusion following 2-h ischemia and the effects on cardiac function, infarcted area, and on apoptosis/autophagy were examined. In addition, the activation of Akt and extracellular receptor kinase (ERK) was analyzed. The findings were compared with those obtained in a further 14 pigs where the highest dose levosimendan was infused after glibenclamide and l-nitro-arginine methyl ester (l-NAME)., Results: Intracoronary 1.5, 5 and 12 μg min(-1) levosimendan caused an increase of segmental shortening, dP/dt(max) and cardiac output of 7.8%, 22.6%, and 31.6%; 7.6%, 16.9%, and 21.6%; 2.8%, 5.9%, and 6.2%, respectively, from values measured at the end of ischemia. The beneficial effects elicited by levosimendan were still evident at the end of reperfusion when the increase of segmental shortening, dP/dt(max) and cardiac output caused by the three doses of levosimendan amounted to 3.7%, 13.3%, and 16.5%; 1.5%, 9.4%, and 11%; 1.4%, 2.7%, and 3.9%, respectively. When doses of 5 and 12 μg min(-1) levosimendan were used, a reduction of infarcted area to about 69% and 67% of area at risk was observed, and was significantly different from that of about 79% measured in control animals. In addition, after intracoronary levosimendan, the inhibition of apoptosis and activation of autophagy and a dose-related increase of the level of phosphorylation of ERK and Akt were observed. These responses were completely prevented by glibenclamide and significantly reduced by l-NAME., Conclusions: The results of this study show that intracoronary levosimendan reduces cell death induced by ischemia/reperfusion in a dose-dependent manner and activates survival signaling through K(ATP) channel opening and NO. These findings support interesting implications for cardioprotection in interventional cardiology and cardiac surgery., (Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.)

Precise evaluation of the cardiac and thoracic anatomy of the patient is mandatory for planning safe minimally invasive direct coronary artery bypass (MIDCAB). Three-dimensional images obtained with a computed tomographic coronary angiography (angio-CT) scan make it possible to accurately visualize the intrathoracic surgical anatomy in order to check the feasibility of the direct exposure of the anatomical structures involved in the surgical procedure. Particular morphological parameters of coronary arteries such as diameter, wall calcification, and intramyocardial position as well as bypass grafts and internal thoracic artery (ITA) displacement can all be precisely defined with this method. We present our preliminary experience using cardiac angio-CT scan as a method for selecting patients for MIDCAB in order to avoid possible surgical complications to minimize the necessity for conversion to the standard surgical approach as well as for choosing the best surgical access.

Objective: To evaluate the possible protective effects of fenoldopam on renal function in patients undergoing cardiopulmonary bypass., Design: Prospective, randomized trial., Setting: University teaching hospital., Participants: One hundred sixty consecutive patients with serum creatinine >1.5 mg/dL who underwent uncomplicated moderate hypothermic cardiopulmonary bypass for cardiac surgery., Interventions: A random group of 80 patients was managed conventionally (group A), whereas another random group of 80 patients received continuous intravenous administration of low-dose fenoldopam (0.1-0.3 microg/kg/min) during cardiopulmonary bypass and in the early postoperative period (group B)., Measurements and Main Results: An improvement of postoperative renal parameters were observed only in group B: preoperative serum creatinine 1.82 +/- 0.2 versus 1.43 +/- 0.73 postoperatively (p < 0.001), preoperative creatinine clearance 51.34 +/- 22.26 versus 67.14 +/- 18.55 postoperatively (p < 0.001)., Conclusions: In this study, fenoldopam was an effective agent in the prevention of renal dysfunction after cardiopulmonary bypass.

A left ventricular aneurysm can develop in patients sustaining blunt chest injury. This condition has been attributed to myocardial contusion or to a direct vascular lesion leading to myocardial necrosis. We report the case of a pseudoaneurysm resulting from myocardial dissection beginning from a small tear in the endocardial wall. Successful surgical exclusion of the pseudoaneurysm by endoaneurysmal patch closure of the communications between the aneurysm and the left ventricular cavity is described.

The efficacy of losulazine was determined in 32 patients with hypertension. Each subject was randomly assigned to receive either losulazine (n = 16) or placebo (n = 16) in a double-blind fashion. Losulazine in the dosage range of 10 to 30 mg b.i.d. effectively lowered the blood pressure. Diastolic blood pressure was lowered to less than or equal to 90 mm Hg in over 70% of the subjects receiving losulazine. There was no evidence of an increase in heart rate; to the contrary, there was a tendency for heart rate to decrease. Six subjects dropped out of the study before completion. Four of these were receiving placebo and dropped out because of lack of efficacy. One subject receiving losulazine dropped out for personal reasons during the first week of the study, and the other subject (also taking losulazine) dropped out when a drug-related pruritus (itchy eyes) developed. This event was readily reversed upon discontinuation of the drug. The drug was well tolerated and side effects were minimal, with no evidence of orthostatic effects or sexual dysfunction. There was a suggestion that nasal stuffiness and conjunctival congestion may be drug related. There were no changes in any laboratory values or body weight.

Acute aortic dissection is a challenging surgical disease. Replacement of the supracoronary aorta alone can be followed by recurrent aneurysm formation at the level of the residual aortic root. The Bentall procedure prevents this late complication but intraoperative haemorrhage may be severe and valve replacement is always mandatory. A new surgical technique is presented which has been adopted in seven consecutive patients with no deaths. With this procedure, strengthening of the aortic root is obtained by inserting three Dacron Double Velour patches "between" the internal and external aortic lamina, one for each sinus of Valsalva. The patches override the coronary ostia which are left wide patent, and are anchored directly to the aortic anulus by single mattress sutures which reduce the size of the anulus. Suspension of the valve leaflets to the patches overriding each other at the commissures together with anuloplasty reestablish valve continency. The two aortic stumps are secured with running sutures over the free edge and a tubular Dacron graft is then anastomosed to them. The procedure reinforces the aortic root, will prevent recurrent aneurysm formation and avoids at the same time valve replacement, when unnecessary, and coronary arteries reimplantation.

The hypothesis that prostaglandins have a modulatory role in adrenergic neurotransmitter release was tested in the anesthetized dog. Inhibition of prostaglandin synthesis with indomethacin (10 mg/kg, i.v.) did not alter positive chronotropic responses to cardioaccelerator nerve stimulation or blood pressure responses to exogenous norepinephrine. In the presence of indomethacin, infusions of PGE, (0.01 and 0.1 microgram kg-1 min-1) also failed to influence the responses to cardioaccelerator nerve stimulation although the blood pressure responses to exogenous norepinephrine were reduced in a dose-related manner. It was concluded that endogenous prostaglandins and exogenous PGE2, the purported physiological inhibitor of neurotransmitter release in cardiac tissue, do not play a role in modulating chronotropic responses during cardioaccelerator nerve stimulation in the anesthetized dog.