Bupropion for the treatment of apathy in Huntington's disease:A multicenter, randomised, double-blind, placebo-controlled, prospective crossover trial

OBJECTIVE:To evaluate the efficacy and safety of bupropion in the treatment of apathy in Huntington's disease (HD). METHODS:In this phase 2b multicentre, double-blind, placebo-controlled crossover trial, individuals with HD and clinical signs of apathy according to the Structured Clinical Interview for Apathy-Dementia (SCIA-D), but not depression (n = 40) were randomized to receive either bupropion 150/300mg or placebo daily for 10 weeks. The primary outcome parameter was a significant change of the Apathy Evaluation Scale (AES) score after ten weeks of treatment as judged by an informant (AES-I) living in close proximity with the study participant. The secondary outcome parameters included changes of 1. AES scores determined by the patient (AES-S) or the clinical investigator (AES-C), 2. psychiatric symptoms (NPI, HADS-SIS, UHDRS-Behavior), 3. cognitive performance (SDMT, Stroop, VFT, MMSE), 4. motor symptoms (UHDRS-Motor), 5. activities of daily function (TFC, UHDRS-Function), and 6. caregiver distress (NPI-D). In addition, we investigated the effect of bupropion on brain structure as well as brain responses and functional connectivity during reward processing in a gambling task using magnetic resonance imaging (MRI). RESULTS:At baseline, there were no significant treatment group differences in the clinical primary and secondary outcome parameters. At endpoint, there was no statistically significant difference between treatment groups for all clinical primary and secondary outcome variables. Study participation, irrespective of the intervention, lessened symptoms of apathy according to the informant and the clinical investigator. CONCLUSION:Bupropion does not alleviate apathy in HD. However, study participation/placebo effects were observed, which document the need for carefully controlled trials when investigating therapeutic interventions for the neuropsychiatric symptoms of HD. TRIAL REGISTRATION:ClinicalTrials.gov 01914965

Evaluation of Electrosurgical Interference to Low-Power Spread-Spectrum Local Area Net Transceivers

Objective. To study whether an electrosurgery device interferes with the operation of a low-power spread-spectrum wireless network adapter. Methods. Nonrandomized, unblinded trials with controls, conducted in the corridor of our institution\u27s operating suite using two portable computers equipped with RoamAbout omnidirectional 250 mW spread-spectrum 928 MHz wireless network adapters. To simulate high power electrosurgery interference, a 100-watt continuous electrocoagulation arc was maintained five feet from the receiving adapter, while device reported signal to noise values were measured at 150 feet and 400 feet distance between the wireless-networked computers. At 150 feet range, and with continuous 100-watt electrocoagulation arc five feet from one computer, error-corrected local area net throughput was measured by sending and receiving a large file multiple times. Results. The reported signal to noise (N = 50) decreased with electrocoagulation from 36.42 ± 3.47 (control) to 31.85 ± 3.64 (electrocoagulation) (p \u3c 0.001) at 400 feet inter-adapter distance, and from 64.53 ± 1.43 (control) to 60.12 ± 3.77 (electrocoagulation) (p \u3c 0.001) at 150 feet inter-adapter distance. There was no statistically significant change in network throughput (average 93 kbyte/ second) at 150 feet inter-adapter distance, either transmitting or receiving during continuous 100 Watt electrocoagulation arc. Conclusions. The manufacturer indicates acceptable performance will be obtained with signal to noise values as low as 20. In view of this, while electrocoagulation affects this spread spectrum network adapter, the effects are small even at 400 feet. At a distance of 150 feet, no discernible effect on network communications was found, suggesting that if other obstructions are minimal, within a wide range on one floor of an operating suite, network communications may be maintained using the technology of this wireless spread spectrum network adapter. The impact of such adapters on cardiac pacemakers should be studied. Wireless spread spectrum network adapters are an attractive technology for mobile computer communications in the operating room

Functional redundancy of mitochondrial enoyl-CoA isomerases in the oxidation of unsaturated fatty acids

Mitochondrial enoyl-CoA isomerase (ECI1) is an auxiliary enzyme involved in unsaturated fatty acid oxidation. In contrast to most of the other enzymes involved in fatty acid oxidation, a deficiency of ECI1 has yet to be identified in humans. We used wild-type (WT) and Eci1-deficient knockout (KO) mice to explore a potential presentation of human ECI1 deficiency. Upon food withdrawal, Eci1-deficient mice displayed normal blood β-hydroxybutyrate levels (WT 1.09 mM vs. KO 1.10 mM), a trend to lower blood glucose levels (WT 4.58 mM vs. KO 3.87 mM, P=0.09) and elevated blood levels of unsaturated acylcarnitines, in particular C12:1 acylcarnitine (WT 0.03 μM vs. KO 0.09 μM, P<0.01). Feeding an olive oil-rich diet induced an even greater increase in C12:1 acylcarnitine levels (WT 0.01 μM vs. KO 0.04 μM, P<0.01). Overall, the phenotypic presentation of Eci1-deficient mice is mild, possibly caused by the presence of a second enoyl-CoA isomerase (Eci2) in mitochondria. Knockdown of Eci2 in Eci1-deficient fibroblasts caused a more pronounced accumulation of C12:1 acylcarnitine on incubation with unsaturated fatty acids (12-fold, P<0.05). We conclude that Eci2 compensates for Eci1 deficiency explaining the mild phenotype of Eci1-deficient mice. Hypoglycemia and accumulation of C12:1 acylcarnitine might be diagnostic markers to identify ECI1 deficiency in humans.-van Weeghel, M., te Brinke, H., van Lenthe, H., Kulik, W., Minkler, P. E., Stoll, M. S. K., Sass, J. O., Janssen, U., Stoffel, W., Schwab, O. K., Wanders, R. J. A., Hoppel, C. L., Houten, S. M. Functional redundancy of mitochondrial enoyl-CoA isomerases in the oxidation of unsaturated fatty acids