The phenotypic and genotypic spectrum of individuals with mono- or biallelic ANK3 variants.

ANK3 encodes ankyrin-G, a protein involved in neuronal development and signaling. Alternative splicing gives rise to three ankyrin-G isoforms comprising different domains with distinct expression patterns. Mono- or biallelic ANK3 variants are associated with non-specific syndromic intellectual disability in 14 individuals (seven with monoallelic and seven with biallelic variants). In this study, we describe the clinical features of 13 additional individuals and review the data on a total of 27 individuals (16 individuals with monoallelic and 11 with biallelic ANK3 variants) and demonstrate that the phenotype for biallelic variants is more severe. The phenotypic features include language delay (92%), autism spectrum disorder (76%), intellectual disability (78%), hypotonia (65%), motor delay (68%), attention deficit disorder (ADD) or attention deficit hyperactivity disorder (ADHD) (57%), sleep disturbances (50%), aggressivity/self-injury (37.5%), and epilepsy (35%). A notable phenotypic difference was presence of ataxia in three individuals with biallelic variants, but in none of the individuals with monoallelic variants. While the majority of the monoallelic variants are predicted to result in a truncated protein, biallelic variants are almost exclusively missense. Moreover, mono- and biallelic variants appear to be localized differently across the three different ankyrin-G isoforms, suggesting isoform-specific pathological mechanisms.

Early mortality in STXBP1-related disorders.

INTRODUCTION: Pathogenic variants in STXBP1 cause a spectrum of disorders mainly consisting of developmental and epileptic encephalopathy (DEE), often featuring drug-resistant epilepsy. An increased mortality risk occurs in individuals with drug-resistant epilepsy and DEE, with sudden unexpected death in epilepsy (SUDEP) often the major cause of death. This study aimed to identify the rate and causes of mortality in STXBP1-related disorders. METHODS: Through an international call, we analyzed data on individuals with STXBP1 pathogenic variants, who passed away from causes related to their disease. RESULTS: We estimated a mortality rate of 3.2% (31/966), based on the STXBP1 Foundation and the STXBP1 Global Connect registry. In total, we analyzed data on 40 individuals (23 males) harboring pathogenic STXBP1 variants, collected from different centers worldwide. They died at a median age of 13 years (range: 11 months-46 years). The most common cause of death was SUDEP (36%), followed by pulmonary infections and respiratory complications (33%). The incidence of SUDEP peaked in mid-childhood, while non-SUDEP causes were more frequent in early childhood or adulthood (p = 0.006). In the most severe phenotypes, death was related to non-SUDEP causes (p = 0.018). CONCLUSION: We found a mortality rate in STXBP1-related disorders similar to other DEEs, with an early age at death and SUDEP as well as pulmonary infections as the main cause of death. These findings assist in prognostic evaluation and genetic counseling for the families. They help to define the mortality risk of STXBP1-related disorders and implement preventative strategies.

IRF2BPL as a novel causative gene for progressive myoclonus epilepsy.

IRF2BPL has recently been described as a novel cause of neurodevelopmental disorders with multisystemic regression, epilepsy, cerebellar symptoms, dysphagia, dystonia, and pyramidal signs. We describe a novel IRF2BPL phenotype consistent with progressive myoclonus epilepsy (PME) in three novel subjects and review the features of the 31 subjects with IRF2BPL-related disorders previously reported. Our three probands, aged 28-40 years, harbored de novo nonsense variants in IRF2BPL (c.370C > T, p.[Gln124*] and c.364C > T; p.[Gln122*], respectively). From late childhood/adolescence, they presented with severe myoclonus epilepsy, stimulus-sensitive myoclonus, and progressive cognitive, speech, and cerebellar impairment, consistent with a typical PME syndrome. The skin biopsy revealed massive intracellular glycogen inclusions in one proband, suggesting a similar pathogenic pathway to other storage disorders. Whereas the two older probands were severely affected, the younger proband had a milder PME phenotype, partially overlapping with some of the previously reported IRF2BPL cases, suggesting that some of them might be unrecognized PME. Interestingly, all three patients harbored protein-truncating variants clustered in a proximal, highly conserved gene region around the "coiled-coil" domain. Our data show that PME can be an additional phenotype within the spectrum of IRF2BPL-related disorders and suggest IRF2BPL as a novel causative gene for PME.

Assessing the landscape of STXBP1-related disorders in 534 individuals.

Disease-causing variants in STXBP1 are among the most common genetic causes of neurodevelopmental disorders. However, the phenotypic spectrum in STXBP1-related disorders is wide and clear correlations between variant type and clinical features have not been observed so far. Here, we harmonized clinical data across 534 individuals with STXBP1-related disorders and analysed 19 973 derived phenotypic terms, including phenotypes of 253 individuals previously unreported in the scientific literature. The overall phenotypic landscape in STXBP1-related disorders is characterized by neurodevelopmental abnormalities in 95% and seizures in 89% of individuals, including focal-onset seizures as the most common seizure type (47%). More than 88% of individuals with STXBP1-related disorders have seizure onset in the first year of life, including neonatal seizure onset in 47%. Individuals with protein-truncating variants and deletions in STXBP1 (n = 261) were almost twice as likely to present with West syndrome and were more phenotypically similar than expected by chance. Five genetic hotspots with recurrent variants were identified in more than 10 individuals, including p.Arg406Cys/His (n = 40), p.Arg292Cys/His/Leu/Pro (n = 30), p.Arg551Cys/Gly/His/Leu (n = 24), p.Pro139Leu (n = 12), and p.Arg190Trp (n = 11). None of the recurrent variants were significantly associated with distinct electroclinical syndromes, single phenotypic features, or showed overall clinical similarity, indicating that the baseline variability in STXBP1-related disorders is too high for discrete phenotypic subgroups to emerge. We then reconstructed the seizure history in 62 individuals with STXBP1-related disorders in detail, retrospectively assigning seizure type and seizure frequency monthly across 4433 time intervals, and retrieved 251 anti-seizure medication prescriptions from the electronic medical records. We demonstrate a dynamic pattern of seizure control and complex interplay with response to specific medications particularly in the first year of life when seizures in STXBP1-related disorders are the most prominent. Adrenocorticotropic hormone and phenobarbital were more likely to initially reduce seizure frequency in infantile spasms and focal seizures compared to other treatment options, while the ketogenic diet was most effective in maintaining seizure freedom. In summary, we demonstrate how the multidimensional spectrum of phenotypic features in STXBP1-related disorders can be assessed using a computational phenotype framework to facilitate the development of future precision-medicine approaches.

The role of laryngeal electromyography in vagus nerve stimulation-related vocal fold dysmotility.

Vagus nerve stimulation (VNS) is a useful tool for drug-resistant epilepsy, but it induces known laryngeal side effects, with a significant role on patients' quality of life. VNS patients may show persistent left vocal fold (LVF) palsy at rest and/or recurrent LVF adduction during stimulation. This study aims at electromyographically evaluating laryngeal muscles abnormalities in VNS patients. We compared endoscopic laryngeal evaluation data in six VNS patients with laryngeal muscle electromyography (LMEMG) carried out on the thyroarytenoid, cricothyroid, posterior cricoarytenoid, and cricopharyngeal muscles. Endoscopy showed LVF palsy at rest in 3/6 patients in whom LMEMG documented a tonic spastic activity with reduced phasic modulation. In four out of six patients with recurrent LVF adduction during VNS activation, LMEMG showed a compound muscle action potential persisting for the whole stimulation. This is the first LMEMG report of VNS-induced motor unit activation via recurrent laryngeal nerve and upper laryngeal nerve stimulation. LMEMG data were could, therefore, be considered consistent with the endoscopic laryngeal examination in all patient.

Sleep disorders in Cornelia de Lange syndrome.

Cornelia de Lange syndrome (CdLS) is a rare genetic disorder characterized by growth retardation, intellectual disability, limb defects, typical facial dysmorphism, and other systemic involvement. Sleep disturbances have been frequently reported in CdLS, but these have not been completely characterized, and prevalence data are conflicting. The aim of this paper is to characterize and determine the prevalence of sleep disorders in CdLS patients by means of a validated questionnaire. From November 2012 to November 2013, we asked 46 consecutive parents/caregivers of CdLS patients aged more than 3 years old to fill out the sleep disturbances scale for children (SDSC). The subjects were also characterized by the presence of epilepsy, intellectual disability (ID), behavioral problems, CdLS severity score, gastroesophageal reflux disease (GERD), and genetic test results. An abnormal total sleep score was found in 7 patients (15.2%), 26 (56.5%) showed a borderline total score, and 18 (39.1%) had an abnormal score for at least one SDSC factor. In our study sleep disorders were found to be positively associated to presence of epilepsy, GERD, ID, and behavioral disturbances. No correlation was evident with specific mutations of the different genes, BMI, and severity score. Our results confirm that sleep disorders represent a common problem in CdLS, with higher incidence than in the normal population. In these patients sleep disorders seem to be more prevalent in comorbid settings, representing a clinical indicator for different medical and neuropsychiatric disorders. Better knowledge and characterization of typology of sleep disorders in CdLS patients could permit a more specific therapeutic approach. © 2016 Wiley Periodicals, Inc.

Laryngeal motility alteration: A missing link between sleep apnea and vagus nerve stimulation for epilepsy.

This study aimed to evaluate the prevalence and the relationship of sleep breathing disorders (SBDs) and laryngeal motility alterations in patients with drug-resistant epilepsy after vagus nerve stimulator (VNS) implantation. Twenty-three consecutive patients with medically refractory epilepsy underwent out-of-center sleep testing before and after VNS implantation. Eighteen eligible subjects underwent endoscopic laryngeal examination post-VNS implantation. Statistical analysis was carried out to assess an association between laryngeal motility alterations and the onset/worsening of SBDs. After VNS implantation, 11 patients showed a new-onset mild/moderate SBD. Half of the patients already affected by obstructive sleep apnea (OSA) showed worsening of SBD. All of the patients with a new-onset OSA had a laryngeal pattern with left vocal cord adduction (LVCA) during VNS stimulation. The association between VNS-induced LVCA and SBD was statistically significant. This study suggests an association between VNS and SBD, hinting to a pivotal role of laryngeal motility alterations. The relationship between SBD and VNS-induced LVCA supports the need to routinely investigate sleep respiratory and laryngeal motility patterns before and after VNS implantation.

Circadian phase typing in idiopathic generalized epilepsy: Dim light melatonin onset and patterns of melatonin secretion-Semicurve findings in adult patients.

OBJECTIVE/BACKGROUND: It has been debated in the literature whether patients with idiopathic generalized epilepsy (IGE) have a distinctive, evening-oriented chronotype. The few questionnaire-based studies that are available in the literature have conflicting results. The aim of our study was to define chronotype in patients with IGE by determining dim light melatonin onset (DLMO). PATIENTS/METHODS: Twenty adults diagnosed with IGE (grand mal on awakening [GM] in 7 cases and juvenile myoclonic epilepsy in 13 cases) were investigated by means of a face-to-face semistructured sleep interview, Morningness-Eveningness Questionnaire (MEQ), Pittsburgh Sleep Quality Index (PSQI) questionnaire, and a melatonin salivary test with DLMO determination. Eighteen healthy subjects (HC) and 28 patients affected with cryptogenic focal epilepsy (FE) served as controls. RESULTS: The mean MEQ score was significantly lower in patients with IGE than that in patients with FE (49.1±5.9 versus 56.1±8.7 P<0.01) but not significantly lower than that in HC (49.1±5.9 versus 49.3±8.6). Midsleep on free days corrected for sleep duration did not differ significantly between the three subject groups (04:59±01:21h, 04:37±01:17h, 04:29±00:52h). The mean DLMO time in patients with IGE (22:13±01:34h) occurred 49min later than that in HC (21.24±1h), and the melatonin surge within the 30-minute time interval after DLMO in patients with IGE was significantly lower than that in HC (1.51±2.7 versus 3.8±3.6pg/mL P=0.045). CONCLUSIONS: Subjective measures of chronotype do not indicate a definite evening-oriented chronotype in patients with IGE. However, the data concerning endogenous melatonin secretion indicate that patients with IGE tend to have a late circadian phase. Further studies are warranted in order to better define the late pattern of endogenous melatonin secretion in patients with IGE and to ascertain the role of this pattern in influencing behavioral chronotype in these subjects.

Controlling the Relaxation Dynamics of Polymer Networks by Combining Associative and Dissociative Dynamic Covalent Bonds.

Dynamic polymer networks offer a promising solution to key challenges in polymers such as recyclability, processability, and damage repair. However, the trade-off between combining facile processability, fast self-healing, and high creep resistance remains a major obstacle to implementation. To overcome this, two very distinct dynamic covalent chemistries, Diels-Alder and transesterification, is combined in a single network. The resulting dual dynamic networks offer an unprecedented set of properties and control over the relaxation times. The system decouples the relaxation dynamics of the network from the spatial motifs, and the tuning of the ratio between chemistries enables to control of the relaxation dynamics over six orders of magnitude. Taking advantage of this control, the composition and rheological behavior is optimized to drastically improve the resolution for extrusion-based additive manufacturing of dynamic covalent networks. Additionally, two well-defined and separated stress relaxation peaks are observed at compositions close to 50% of each dynamic chemistry, accentuating the double character of the system's relaxation dynamics. This atypical situation, enables to preparation of self-healing materials with negligible creep, and with shape-memory properties solely leveraging the two distinct relaxation dynamics, instead of the glass transition temperature or the melting point.

Emergence of lingual dystonia and strabismus in early-onset SCN8A self-limiting familial infantile epilepsy.

Pathogenic variants in SCN8A are associated with a broad phenotypic spectrum, including Self-Limiting Familial Infantile Epilepsy (SeLFIE), characterized by infancy-onset age-related seizures with normal development and cognition. Movement disorders, particularly paroxysmal kinesigenic dyskinesia typically arising after puberty, may represent another core symptom. We present the case of a 1-year-old girl with a familial disposition to self-limiting focal seizures from the maternal side and early-onset orofacial movement disorders associated with SCN8A-SeLFIE. Brain MRI was normal. Genetic testing revealed a maternally inherited SCN8A variant [c.4447G > A; p.(Glu1483Lys)]. After the introduction of valproic acid, she promptly achieved seizure control as well as complete remission of strabismus and a significant decrease in episodes of tongue deviation. Family history, genetic findings, and epilepsy phenotype are consistent with SCN8A-SeLFIE. Movement disorders are an important part of the SCN8A phenotypic spectrum, and this case highlights the novel early-onset orofacial movement disorders associated with this condition. The episodes of tongue deviation and protrusion suggest focal oromandibular (lingual) dystonia. Additionally, while infantile strabismus or esophoria is a common finding in healthy individuals, our case raises the possibility of an ictal origin of the strabismus. This study underscores the importance of recognizing and addressing movement disorders in SCN8A-SeLFIE patients, particularly the rare early-onset orofacial manifestations. It adds to the growing body of knowledge regarding the diverse clinical presentations of SCN8A-associated disorders and suggests potential avenues for clinical management and further research.

Epilepsy as a Novel Phenotype of BPTF-Related Disorders.

BACKGROUND: Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (NEDDFL) is associated to BPTF gene haploinsufficiency. Epilepsy was not included in the initial descriptions of NEDDFL, but emerging evidence indicates that epileptic seizures occur in some affected individuals. This study aims to investigate the electroclinical epilepsy features in individuals with NEDDFL. METHODS: We enrolled individuals with BPTF-related seizures or interictal epileptiform discharges (IEDs) on electroencephalography (EEG). Demographic, clinical, genetic, raw EEG, and neuroimaging data as well as response to antiseizure medication were assessed. RESULTS: We studied 11 individuals with a null variant in BPTF, including five previously unpublished ones. Median age at last observation was 9 years (range: 4 to 43 years). Eight individuals had epilepsy, one had a single unprovoked seizure, and two showed IEDs only. Key features included (1) early childhood epilepsy onset (median 4 years, range: 10 months to 7 years), (2) well-organized EEG background (all cases) and brief bursts of spikes and slow waves (50% of individuals), and (3) developmental delay preceding seizure onset. Spectrum of epilepsy severity varied from drug-resistant epilepsy (27%) to isolated IEDs without seizures (18%). Levetiracetam was widely used and reduced seizure frequency in 67% of the cases. CONCLUSIONS: Our study provides the first characterization of BPTF-related epilepsy. Early-childhood-onset epilepsy occurs in 19% of subjects, all presenting with a well-organized EEG background associated with generalized interictal epileptiform abnormalities in half of these cases. Drug resistance is rare.

Sleep and sleep disorders during pregnancy and postpartum: The Life-ON study.

OBJECTIVE: to prospectively assess sleep and sleep disorders during pregnancy and postpartum in a large cohort of women. METHODS: multicenter prospective Life-ON study, recruiting consecutive pregnant women at a gestational age between 10 and 15 weeks, from the local gynecological departments. The study included home polysomnography performed between the 23rd and 25th week of pregnancy and sleep-related questionnaires at 9 points in time during pregnancy and 6 months postpartum. RESULTS: 439 pregnant women (mean age 33.7 ± 4.2 yrs) were enrolled. Poor quality of sleep was reported by 34% of women in the first trimester of pregnancy, by 46% of women in the third trimester, and by as many as 71% of women in the first month after delivery. A similar trend was seen for insomnia. Excessive daytime sleepiness peaked in the first trimester (30% of women), and decreased in the third trimester, to 22% of women. Prevalence of restless legs syndrome was 25%, with a peak in the third trimester of pregnancy. Polysomnographic data, available for 353 women, revealed that 24% of women slept less than 6 h, and 30.6% of women had a sleep efficiency below 80%. Sleep-disordered breathing (RDI≥5) had a prevalence of 4.2% and correlated positively with BMI. CONCLUSIONS: The Life-ON study provides the largest polysomnographic dataset coupled with longitudinal subjective assessments of sleep quality in pregnant women to date. Sleep disorders are highly frequent and distributed differently during pregnancy and postpartum. Routine assessment of sleep disturbances in the perinatal period is necessary to improve early detection and clinical management.

Natural History Study of STXBP1-Developmental and Epileptic Encephalopathy Into Adulthood.

BACKGROUND AND OBJECTIVES: Pathogenic STXBP1 variants cause a severe early-onset developmental and epileptic encephalopathy (STXBP1-DEE). We aimed to investigate the natural history of STXBP1-DEE in adults focusing on seizure evolution, the presence of movement disorders, and the level of functional (in)dependence. METHODS: In this observational study, patients with a minimum age of 18 years carrying a (likely) pathogenic STXBP1 variant were recruited through medical genetics departments and epilepsy centers. Treating clinicians completed clinical questionnaires and performed semistructured video examinations while performing tasks from the (modified) Unified Parkinson Disease Rating Scale when possible. RESULTS: Thirty adult patients were included for summary statistics, with video recordings available for 19 patients. The median age at last follow-up was 24 years (range 18-58 years). All patients had epilepsy, with a median onset age of 3.5 months. At last follow-up, 80% of adults had treatment-resistant seizures despite long periods of seizure freedom in 37%. Tonic-clonic, focal, and tonic seizures were most frequent in adults. Epileptic spasms, an unusual feature beyond infancy, were present in 3 adults. All individuals had developmental impairment. Periods of regression were present in 59% and did not always correlate with flare-ups in seizure activity. Eighty-seven percent had severe or profound intellectual disability, 42% had autistic features, and 65% had significant behavioral problems. Video examinations showed gait disorders in all 12 patients able to walk, including postural abnormalities with external rotation of the feet, broad-based gait, and asymmetric posture/dystonia. Tremor, present in 56%, was predominantly of the intention/action type. Stereotypies were seen in 63%. Functional outcome concerning mobility was variable ranging from independent walking (50%) to wheelchair dependence (39%). Seventy-one percent of adults were nonverbal, and all were dependent on caregivers for most activities of daily living. DISCUSSION: STXBP1-DEE warrants continuous monitoring for seizures in adult life. Periods of regression are more frequent than previously established and can occur into adulthood. Movement disorders are often present and involve multiple systems. Although functional mobility is variable in adulthood, STXBP1-DEE frequently leads to severe cognitive impairments and a high level of functional dependence. Understanding the natural history of STXBP1-DEE is important for prognostication and will inform future therapeutic trials.

Unexpected Neurological Symptoms of Ruxolitinib: A Case Report.

Ruxolitinib is a highly potent JAK2 inhibitor approved for the treatment of myelofibrosis (idiopathic or post-polycythemia vera or post-essential thrombocythemia) and, more recently, for polycythemia vera with an inadequate response to or intolerant of hydroxyurea. The most common adverse events of ruxolitinib include immunosuppression with an increased risk of reactivation of silent infections and increased non-melanoma skin cancer. The known neurological side effects of ruxolitinib are dizziness and headache, but no neurological paroxysmal episodes have been recorded. This report deals with an 80-year-old outpatient woman with polycythemia vera turned into myelofibrosis who experienced neurological episodes of hypoesthesia and weakness of right arm and leg during ruxolitinib treatment.

Tissue doppler imaging can be useful to distinguish pathological from physiological left ventricular hypertrophy: a study in master athletes and mild hypertensive subjects.

BACKGROUND: Transthoracic echocardiography left ventricular wall thickness is often increased in master athletes and it results by intense physical training. Left Ventricular Hypertrophy can also be due to a constant pressure overload. Conventional Pulsed Wave (PW) Doppler analysis of diastolic function sometimes fails to distinguish physiological from pathological LVH.The aim of this study is to evaluate the role of Pulsed Wave Tissue Doppler Imaging in differentiating pathological from physiological LVH in the middle-aged population. METHODS: we selected a group of 80 master athletes, a group of 80 sedentary subjects with essential hypertension and an apparent normal diastolic function at standard PW Doppler analysis. The two groups were comparable for increased left ventricular wall thickness and mass index (134.4 +/- 19.7 vs 134.5 +/- 22.1 gr/m2; p > .05). Diastolic function indexes using the PW technique were in the normal range for both. RESULTS: Pulsed Wave TDI study of diastolic function immediately distinguished the two groups. While in master athletes the diastolic TDI-derived parameters remained within normal range (E' 9.4 +/- 3.1 cm/sec; E/E' 7.8 +/- 2.1), in the hypertensive group these parameters were found to be constantly altered, with mean values and variation ranges always outside normal validated limits (E' 7.2 +/- 2.4 cm/sec; E/E' 10.6 +/- 3.2), and with E' and E/E' statistically different in the two groups (p < .001). CONCLUSION: Our study showed that the TDI technique can be an easy and validated method to assess diastolic function in differentiating normal from pseudonormal diastolic patterns and it can distinguish physiological from pathological LVH emphasizing the eligibility certification required by legal medical legislation as in Italy.

A case of modern management of Morgagni-Adam-Stokes syndrome.

Transient loss of consciousness initially diagnosed as epileptic seizures and then documented as paroxysmal atrioventricular block. Cardiac resynchronization and defibrillator therapy guided by a multimodality approach.

Cardiac incoordination induced by left bundle branch block: its relation with left ventricular systolic function in patients with and without cardiomyopathy.

BACKGROUND: Although left bundle branch block (LBBB) alters the electrical activation of the heart, it is unknown how it might change the process of myocardial coordination (MC) and how it may affect the left ventricular (LV) systolic function. The present study assessed the effects of LBBB on MC in patients with LBBB with and without dilated (DCMP) or ischemic cardiomyopathy (ICMP). METHODS: Tissue Doppler echocardiography (TDE) was performed in 86 individuals: 21 with isolated LBBB, 26 patients with DCMP + LBBB, 19 patients with ICMP + LBBB and in 20 healthy individuals (Controls). MC was assessed analyzing the myocardial velocity profiles obtained from six basal segments of the LV using TDE. The LV systolic function was assessed by standard two-dimensional echocardiography and by TDE. RESULTS: Severe alterations in MC were observed in subjects with LBBB as compared with controls (P < 0.01 for all comparisons); these derangements were even worse in patients with DCMP and ICMP (P < 0.001 for comparisons with Controls and P < 0.01 for comparison with individuals with isolated LBBB). Some parameters of MC differed significantly between DCMP and ICMP (P < 0.01). A good or very good correlation coefficient was found between variables of MC and variables of LV systolic function. CONCLUSION: LBBB induces severe derangement in the process of MC that are more pronounced in patients with cardiomyopathies and that significantly correlates with the LV systolic function. The assessment of MC may help in the evaluation of the etiology of dilated cardiomyopathy.

First-in-man Percutaneous LAA Closure With an Amplatzer Amulet and TriGuard Embolic Protection Device in a Patient With LAA Thrombus.

Percutaneous left atrial appendage (LAA) closure is currently utilized for the prophylaxis of thromboembolic cerebrovascular accidents in patients with non-valvular atrial fibrillation. The presence of LAA thrombus is usually considered a contraindication for the procedure, since there is a high risk of thrombus embolization. While reports in the literature have shown the feasibility of LAA closure in the presence of LAA thrombus with certain cerebral embolic protection devices, we present the first-in-man LAA closure of a patient with LAA thrombus using the TriGuard Embolic Protection Device.

A Novel Technique for Prosthetic Valve Retrieval After Transcatheter Aortic Valve Embolization.

Although the rate of procedural complications during transcatheter aortic valve implantation has decreased because of technological advancement and increased operator experience, device embolization remains a rare but potentially fatal complication, even with new generation devices. We report, to our knowledge, the first case of Portico valve (St Jude Medical, Minneapolis, MN) migration despite apparent optimal initial implantation depth, which was retrieved using a novel strategy after failure of a traditional retrieval technique. We also describe a mechanism of left coronary artery systolic perfusion with diastolic backflow, which led to myocardial ischemia.