3 results
The Allure of High-Risk Rewards in Huntington’s disease
- Nelleke C. van Wouwe, Kristen E. Kanoff, Daniel O. Claassen, K. Richard Ridderinkhof, Peter Hedera, Madaline B. Harrison, Scott A. Wylie
-
- Journal:
- Journal of the International Neuropsychological Society / Volume 22 / Issue 4 / April 2016
- Published online by Cambridge University Press:
- 28 December 2015, pp. 426-435
-
- Article
- Export citation
-
Objectives: Huntington’s disease (HD) is a neurodegenerative disorder that produces a bias toward risky, reward-driven decisions in situations where the outcomes of decisions are uncertain and must be discovered. However, it is unclear whether HD patients show similar biases in decision-making when learning demands are minimized and prospective risks and outcomes are known explicitly. We investigated how risk decision-making strategies and adjustments are altered in HD patients when reward contingencies are explicit. Methods: HD (N=18) and healthy control (HC; N=17) participants completed a risk-taking task in which they made a series of independent choices between a low-risk/low reward and high-risk/high reward risk options. Results: Computational modeling showed that compared to HC, who showed a clear preference for low-risk compared to high-risk decisions, the HD group valued high-risks more than low-risk decisions, especially when high-risks were rewarded. The strategy analysis indicated that when high-risk options were rewarded, HC adopted a conservative risk strategy on the next trial by preferring the low-risk option (i.e., they counted their blessings and then played the surer bet). In contrast, following a rewarded high-risk choice, HD patients showed a clear preference for repeating the high-risk choice. Conclusions: These results indicate a pattern of high-risk/high-reward decision bias in HD that persists when outcomes and risks are certain. The allure of high-risk/high-reward decisions in situations of risk certainty and uncertainty expands our insight into the dynamic decision-making deficits that create considerable clinical burden in HD. (JINS, 2016, 22, 426–435)
Tetrathiomolybdate versus Trientine in the Initial Treatment of Neurologic Wilson's Disease
-
- By George J. Brewer, Department of Human Genetics, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA, Fred Askari, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA, Matthew T. Lorincz, Department of Neurology, University of Michigan, Ann Arbor, MI, USA, Martha Carlson, Department of Pediatrics-Neurology, University of Michigan, Ann Arbor, MI, USA, Michael Schilsky, Department of Internal Medicine, Cornell University, New York, NY, USA, Karen J. Kluin, Department of Neurology, Department of Speech Pathology, University of Michigan, Ann Arbor, MI, USA, Peter Hedera, Department of Neurology, Vanderbilt University, Nashville, TN, USA, Paolo Moretti, Departments of Neurology and Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA, John K. Fink, Department of Neurology, University of Michigan, Ann Arbor, MI, USA, Roberta Tankanow, College of Pharmacy, University of Michigan, Ann Arbor, MI, USA, Robert B. Dick, Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA, Julia Sitterly, Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA
- Edited by Jeffrey L. Cummings
-
- Book:
- Progress in Neurotherapeutics and Neuropsychopharmacology
- Published online:
- 13 May 2010
- Print publication:
- 06 March 2008, pp 153-166
-
- Chapter
- Export citation
-
Summary
ABSTRACT
Background: The initial treatment of the neurologic presentation of Wilson's disease is problematic. Penicillamine, used for years on most patients, causes neurologic worsening in up to half of such patients, and half of those who worsen never recover. Zinc, ideal for maintenance therapy, is too slow for these acutely ill patients. We have developed tetrathiomolybdate (TM) for this type of patient, and it has worked well in open label studies. Trientine, another anticopper drug on the market approved for penicillamine intolerant patients, had not been tried in this type of patient. Here, we report on a double blind trial of TM versus trientine in the neurologically presenting Wilson's disease patient. Design and Methods: The study was a double blind design in which patients received either TM plus zinc, or trientine plus zinc, for 8 weeks. Patients were accepted if they presented with neurologic symptoms from Wilson's disease, if they had not been treated longer than 4 weeks with penicillamine or trientine. Patients were followed in the hospital for the 8 weeks of treatment with weekly semiquantitative neurologic and speech examinations, to evaluate possible neurologic worsening. They also had blood and urine studies done weekly. At discharge from hospital they were continued on zinc maintenance therapy, and returned at yearly intervals for 3 years for further evaluation. Results: Twenty-three patients were entered into the trientine arm and 6 reached criteria for neurologic deterioration, while 25 patients were entered into the TM arm and only 1 deteriorated (p < 0.05).
Tetrathiomolybdate versus Trientine in the Initial Treatment of Neurologic Wilson's Disease
- George J. Brewer, Fred Askari, Matthew T. Lorincz, Martha Carlson, Michael Schilsky, Karen J. Kluin, Peter Hedera, Paolo Moretti, John K. Fink, Roberta Tankanow, Robert B. Dick, Julia Sitterly
-
- Journal:
- Progress in Neurotherapeutics and Neuropsychopharmacology / Volume 3 / Issue 1 / January 2008
- Published online by Cambridge University Press:
- 08 June 2007, pp. 153-165
- Print publication:
- January 2008
-
- Article
- Export citation
-
ABSTRACT
Background: The initial treatment of the neurologic presentation of Wilson's disease is problematic. Penicillamine, used for years on most patients, causes neurologic worsening in up to half of such patients, and half of those who worsen never recover. Zinc, ideal for maintenance therapy, is too slow for these acutely ill patients. We have developed tetrathiomolybdate (TM) for this type of patient, and it has worked well in open label studies. Trientine, another anticopper drug on the market approved for penicillamine intolerant patients, had not been tried in this type of patient. Here, we report on a double blind trial of TM versus trientine in the neurologically presenting Wilson's disease patient. Design and Methods: The study was a double blind design in which patients received either TM plus zinc, or trientine plus zinc, for 8 weeks
This study was originally published in reference 1. Patients were accepted if they presented with neurologic symptoms from Wilson's disease, if they had not been treated longer than 4 weeks with penicillamine or trientine. Patients were followed in the hospital for the 8 weeks of treatment with weekly semiquantitative neurologic and speech examinations, to evaluate possible neurologic worsening. They also had blood and urine studies done weekly. At discharge from hospital they were continued on zinc maintenance therapy, and returned at yearly intervals for 3 years for further evaluation. Results: Twenty-three patients were entered into the trientine arm and 6 reached criteria for neurologic deterioration, while 25 patients were entered into the TM arm and only 1 deteriorated (p < 0.05). One patient on trientine had an adverse event while 7 on TM had adverse events. All adverse events were mild. Four patients in the trientine arm died during follow-up, 3 having shown initial neurologic deterioration, 2 patients in the TM arm died. In those patients who did not deteriorate or die, neurologic and speech recovery over 3 years was good. Interpretation: TM is a superior choice to trientine for the initial therapy of neurologic Wilson's disease.