New onset left frontal lobe seizure presenting with ictal asystole

AbstractIctal asystole is a presumably rare but potentially fatal complication of seizures, most often of temporal lobe origin. It is believed that at least some cases of sudden unexplained death in epilepsy (SUDEP) might be triggered by ictal bradycardia or asystole. Current standard practice is to implant a permanent pacemaker in these patients to prevent syncope and/or death. However, emerging data suggests that effective medical or surgical treatment of epilepsy might be enough to prevent cardiac asystole, eliminating the need for permanent pacemaker placement. We describe a case of new onset left frontal lobe epilepsy in a young athletic patient who presented with near-syncopal episodes but whose comprehensive work-up revealed frequent events of ictal bradycardia and asystole. He responded well to monotherapy using oxcarbazepine, avoiding a permanent pacemaker

Clinical outcomes after upgrading from pacemakers to cardiac resynchronization therapy

Background and Aims: Right ventricular pacing may lead to heart failure (HF). Upgrades from pacemakers to cardiac resynchronization therapy (CRT) were excluded from most randomized, controlled trials. We sought to determine the long-term outcomes of upgrading from pacemakers to CRT with (CRT-D) or without (CRT-P) defibrillation in patients with no history of sustained ventricular arrhythmias. Methods and Results: In this observational study, clinical events were quantified in relation to the type of implant (de novo or upgrade) and device type at upgrade (CRT-P or CRT-D). Patients underwent CRT implantation (n = 1,545; 1,314 [85%] de novo implants and 231 [15%] upgrades) over a median of 4.6 years [interquartile range: 2.4 - 7.0]). In analyses of crude event rates, upgrades had a higher total mortality (adjusted hazard ratio [aHR]: 1.33; 95% confidence interval [CI] 0.10-1.61), a higher total mortality or HF hospitalization (aHR: 1.26; 95% CI 1.05-1.51), but similar mortality or hospitalization for major adverse cardiac events (MACEs, aHR: 1.15; 95% CI 0.96-1.38). No group differences emerged in any of these endpoints after propensity score matching. After inverse probability weighting in upgrades, total mortality (HR: 0.55; 95% CI 0.36-0.73), total mortality or HF hospitalization (HR: 0.56; 95% CI 0.34-0.79) and total mortality or hospitalization for MACEs (HR: 0.61; 95% CI 0.40-0.82) were lower after CRT-D than after CRT-P. Conclusion: Upgrading from pacemakers to CRT was associated with a similar long-term risk of mortality and morbidity to de novo CRT. After upgrade, CRT-D was CRT-D was associated with lower mortality than CRT-

Prospective observational study of implantable cardioverter-defibrillators in primary prevention of sudden cardiac death: study design and cohort description

BACKGROUND: Primary-prevention implantable cardioverter-defibrillators (ICDs) reduce total mortality in patients with severe left ventricular systolic function. However, only a minority of patients benefit from these devices. We designed the Prospective Observational Study of Implantable Cardioverter-Defibrillators (PROSE-ICD) to identify risk factors and enhance our understanding of the biological mechanisms that predispose to arrhythmic death in patients undergoing ICD implantation for primary prevention of sudden death. METHODS AND RESULTS: This is a multicenter prospective cohort study with a target enrollment of 1200 patients. The primary end point is ICD shocks for adjudicated ventricular tachyarrhythmias. The secondary end point is total mortality. All patients undergo a comprehensive evaluation including history and physical examination, signal-averaged electrocardiograms, and blood sampling for genomic, proteomic, and metabolomic analyses. Patients are evaluated every 6 months and after every known ICD shock for additional electrocardiographic and blood sampling. As of December 2011, a total of 1177 patients have been enrolled with more nonwhite and female patients compared to previous randomized trials. A total of 143 patients have reached the primary end point, whereas a total of 260 patients died over an average follow-up of 59 months. The PROSE-ICD study represents a real-world cohort of individuals with systolic heart failure receiving primary-prevention ICDs. CONCLUSIONS: Extensive electrophysiological and structural phenotyping as well as the availability of serial DNA and serum samples will be important resources for evaluating novel metrics for risk stratification and identifying patients at risk for arrhythmic sudden death. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov/ Unique Identifier: NCT00733590.This work was supported in part by the Donald W. Reynolds Cardiovascular Foundation and NIH R01 HL091062 (to G.F.T.).S

A Marfan syndrome‐like phenotype caused by a neocentromeric supernumerary ring chromosome 15

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135625/1/ajmga38000.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135625/2/ajmga38000_am.pd

Breakpoint mapping and haplotype analysis of translocation t(1;12)(q43;q21.1) in two apparently independent families with vascular phenotypes

Background The risk of serious congenital anomaly for de novo balanced translocations is estimated to be at least 6%. We identified two apparently independent families with a balanced t(1;12)(q43;q21.1) as an outcome of a ''Systematic Survey of Balanced Chromosomal Rearrangements in Finns. ''In the first family, carriers (n=6) manifest with learning problems in childhood, and later with unexplained neurological symptoms (chronic headache, balance problems, tremor, fatigue) and cerebral infarctions in their 50s. In the second family, two carriers suffer from tetralogy of Fallot, one from transient ischemic attack and one from migraine. The translocation cosegregates with these vascular phenotypes and neurological symptoms. Methods and Results We narrowed down the breakpoint regions using mate pair sequencing. We observed conserved haplotypes around the breakpoints, pointing out that this translocation has arisen only once. The chromosome 1 breakpoint truncates a CHRM3 processed transcript, and is flanked by the 5 end of CHRM3 and the 3 end of RYR2. TRHDE, KCNC2, and ATXN7L3B flank the chromosome 12 breakpoint. Conclusions This study demonstrates a balanced t(1;12)(q43;q21.1) with conserved haplotypes on the derived chromosomes. The translocation seems to result in vascular phenotype, with or without neurological symptoms, in at least two families. We suggest that the translocation influences the positional expression of CHRM3, RYR2,TRHDE, KCNC2, and/or ATXN7L3B.Peer reviewe

SNP genotyping to screen for a common deletion in CHARGE Syndrome

BACKGROUND: CHARGE syndrome is a complex of birth defects including coloboma, choanal atresia, ear malformations and deafness, cardiac defects, and growth delay. We have previously hypothesized that CHARGE syndrome could be caused by unidentified genomic microdeletion, but no such deletion was detected using short tandem repeat (STR) markers spaced an average of 5 cM apart. Recently, microdeletion at 8q12 locus was reported in two patients with CHARGE, although point mutation in CHD7 on chromosome 8 was the underlying etiology in most of the affected patients. METHODS: We have extended our previous study by employing a much higher density of SNP markers (3258) with an average spacing of approximately 800 kb. These SNP markers are diallelic and, therefore, have much different properties for detection of deletions than STRs. RESULTS: A global error rate estimate was produced based on Mendelian inconsistency. One marker, rs431722 exceeded the expected frequency of inconsistencies, but no deletion could be demonstrated after retesting the 4 inconsistent pedigrees with local flanking markers or by FISH with the corresponding BAC clone. Expected deletion detection (EDD) was used to assess the coverage of specific intervals over the genome by deriving the probability of detecting a common loss of heterozygosity event over each genomic interval. This analysis estimated the fraction of unobserved deletions, taking into account the allele frequencies at the SNPs, the known marker spacing and sample size. CONCLUSIONS: The results of our genotyping indicate that more than 35% of the genome is included in regions with very low probability of a deletion of at least 2 Mb

Role of the autophagic-lysosomal system on low potassium-induced apoptosis in cultured cerebellar granule cells

Apoptotic and autophagic cell death have been implicated, on the basis of morphological and biochemical criteria, in neuronal loss occurring in neurodegenerative diseases and it has been shown that they may overlap. We have studied the relationship between apoptosis and autophagic cell death in cerebellar granule cells (CGCs) undergoing apoptosis following serum and potassium deprivation. We found that apoptosis is accompanied by an early and marked proliferation of autophagosomal-lysosomal compartments as detected by electron microscopy and immunofluorescence analysis. Autophagy is blocked by hrIGF-1 and forskolin, two well-known inhibitors of CGC apoptosis, as well as by adenovirus-mediated overexpression of Bcl-2. 3-Methyladenine (3-MA) an inhibitor of autophagy, not only arrests this event but it also blocks apoptosis. The neuroprotective effect of 3-MA is accompanied by block of cytochrome c (cyt c) release in the cytosol and by inhibition of caspase-3 activation which, in turn, appears to be mediated by cathepsin B, as CA074-Me, a selective inhibitor of this enzyme, fully blocks the processing of pro-caspase-3. Immunofluorescence analysis demonstratesd that cathepsin B, normally confined inside the lysosomal-endosomal compartment, is released during apoptosis into the cytosol where this enzyme may act as an execution protease. Collectively, these observations indicate that autophagy precedes and is causally connected with the subsequent onset of programmed death

An Integrated Decision Making Approach for Adaptive Shared Control of Mobility Assistance Robots

© 2016, Springer Science+Business Media Dordrecht. Mobility assistance robots provide support to elderly or patients during walking. The design of a safe and intuitive assistance behavior is one of the major challenges in this context. We present an integrated approach for the context-specific, on-line adaptation of the assistance level of a rollator-type mobility assistance robot by gain-scheduling of low-level robot control parameters. A human-inspired decision-making model, the drift-diffusion Model, is introduced as the key principle to gain-schedule parameters and with this to adapt the provided robot assistance in order to achieve a human-like assistive behavior. The mobility assistance robot is designed to provide (a) cognitive assistance to help the user following a desired path towards a predefined destination as well as (b) sensorial assistance to avoid collisions with obstacles while allowing for an intentional approach of them. Further, the robot observes the user long-term performance and fatigue to adapt the overall level of (c) physical assistance provided. For each type of assistance a decision-making problem is formulated that affects different low-level control parameters. The effectiveness of the proposed approach is demonstrated in technical validation experiments. Moreover, the proposed approach is evaluated in a user study with 35 elderly persons. Obtained results indicate that the proposed gain-scheduling technique incorporating ideas of human decision-making models shows a general high potential for the application in adaptive shared control of mobility assistance robots