Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia: Review of Clinical Manifestations as Foundations for Therapeutic Development

A comprehensive review of published literature was conducted to elucidate the genetics, neuropathology, imaging findings, prevalence, clinical course, diagnosis/clinical evaluation, potential biomarkers, and current and proposed treatments for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a rare, debilitating, and life-threatening neurodegenerative disorder for which disease-modifying therapies are not currently available. Details on potential efficacy endpoints for future interventional clinical trials in patients with ALSP and data related to the burden of the disease on patients and caregivers were also reviewed. The information in this position paper lays a foundation to establish an effective clinical rationale and address the clinical gaps for creation of a robust strategy to develop therapeutic agents for ALSP, as well as design future clinical trials, that have clinically meaningful and convergent endpoints

Tako-Tsubo Cardiomyopathy during a series of Electroconvulsive Therapy (ECT) applications: A case report, systematic literature research and discussion of specific risk factors

Background Tako-Tsubo Cardiomyopathy (TTC) is an acute, reversible disease of the myocardium. It seems to be caused by an excess of epinephrine, norepinephrine and dopamine. Psychological or physiological stress is considered as a risk factor. Several cases of Tako-Tsubo cardiomyopathy in the context of seizures and electroconvulsive therapy have been reported. Methods We describe the case of a 63-year-old patient who developed TTC during a second series of ECT applications with etomidate anaesthesia and continued antidepressant medication with tranylcypromine. Potential pathophysiological correlations are discussed on the basis of the available literature. Given the increased risk of TTC recurrence, the question on reinitiation of ECT treatment after remission of the heart disease is also addressed. Results At least in theory, depressive disorders, ECT applications with seizures, the application of the anaesthetic etomidate, as well as tranylcypromine treatment may all be causally related to the development of TTC. Etomidate is known to interfere with cortisol synthesis, resulting in sympathomimetic and pro-inflammatory effects. To date, 19 cases of TTC in conjunction with ECT applications have been published. As in our patient, ECT was reinitiated successfully without complications in eight of them. Discussion ECT-related TTC seems to be caused by multiple factors. Circumstantial evidence in our case as well as published data does not support the conclusion that a single risk factor can be held responsible for the development of TTC. Based on theoretical considerations and preliminary findings on a potential role of a relative cortisol deficit, future studies should be encouraged to provide relevant evidence. If careful risk-benefit considerations are done and specific precautions are taken, previous TTC does not exclude reinitiation of ECT

Atrial pacing for prevention of atrial fibrillation: assessment of simultaneously implemented algorithms

Aims Several preliminary studies indicated that right atrial pacing could prevent atrial tachyarrhythmias (ATA). We sought to compare the safety and the efficacy of atrial-based pacing supplemented by dedicated combined algorithms with conventional atrial pacing in the prevention of ATA. Methods Fifty-five patients with a history of recurrent paroxysmal ATA implanted with a dual-chamber pacemaker were studied during two randomized cross-over pacing periods (conventional DDD and DDD with ATA prevention algorithms) of 6 months duration. The primary endpoint was the burden of ATA episodes recorded by the device mode switch algorithm. Results The cross-over analysis did not demonstrate any significant difference between the two pacing modes: 254+/-533 h of ATA during the control period versus 238+/-518 h during the ATA prevention period. Analysis of a subgroup of patients found that those with the lower percentage of ventricular pacing benefited from ATA prevention algorithms (120+/-182 h versus 225+/-350 h during thecontrot period; P<0.04). Conclusion When compared with DDD pacing at 70 bpm, ATA prevention algorithms have not demonstrated significant efficacy. However, a subgroup of patients with preserved native AV conduction (low percentage of ventricular pacing) responded to ATA prevention algorithms. (C) 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved