What is the optimum thiamine dose to treat or prevent Wernicke's encephalopathy or Wernicke-Korsakoff syndrome? Results of a randomized controlled trial.

BACKGROUND: The primary cause of Wernicke-Korsakoff syndrome (WKS) is thiamine deficiency, and more than 90% of cases are reported in alcohol-dependent patients. While observational studies show parenteral thiamine administration drastically reduced WKS-related mortality, relevant treatment trials have never been conducted to determine the optimum thiamine dose. METHODS: Two double-blind, parallel groups, randomized controlled trials (RCTs) were conducted to determine the optimal thiamine dose required for (1) the prevention of Wernicke's encephalopathy (WE), the acute phase of WKS, in asymptomatic but "at-risk" alcohol misuse patients (Study 1) and (2) the treatment of WE in symptomatic alcohol misuse patients (Study 2). Each study had a dosage regimen comprising three parenteral thiamine doses that were allocated at a ratio of 1:1:1. Study 1: Asymptomatic At-Risk patients (N = 393) received either 100 mg daily, 100 mg thrice daily, or 300 mg thrice daily, for 3 days. Study 2: Symptomatic patients (N = 127) received either 100 mg thrice daily, 300 mg thrice daily, or 500 mg thrice daily, for 5 days. Cognitive function was the primary outcome, assessed using the Rowland Universal Dementia Assessment Scale, two Cogstate subtests, and an adapted Story Memory Recall test. Secondary analyses examined differences in neurological function (ataxia, oculomotor abnormalities, and confusion) at follow-up. RESULTS: No significant differences were observed between any of the dosage conditions for either Study 1 or Study 2 on cognition or neurological functioning. This real-world study found that having a clinically unwell target population with high comorbidity and multiple presentations, coupled with challenges in cross-cultural assessment is likely to complicate RCT findings. CONCLUSIONS: The results of this study showed no clear benefit of high dose thiamine over intermediate or lower doses of thiamine, over the time intervals examined, for the treatment and prevention of cognitive and neurological abnormalities related to WKS. Several study limitations temper the interpretation of these findings. Nevertheless, the absence of conclusive evidence for the superiority of high-dose thiamine supports a recommendation for patient-specific treatment, while ensuring that the potential impact of other biochemical factors (e.g., magnesium and other B vitamin deficiencies) are considered and corrected if necessary.

Exploring the reliability and acceptability of cognitive tests for Indigenous Australians: a pilot study.

BACKGROUND: Reliable cognitive assessment for Indigenous Australians is difficult given that mainstream tests typically rely on Western concepts, content and values. A test's psychometric properties should therefore be assessed prior to use in other cultures. The aim of this pilot study was to examine the reliability and acceptability of four cognitive tests for Australian Aboriginal people. METHODS: Participants were 40 male and 44 female (N = 84) Aboriginal patients from Alice Springs Hospital. Four tests were assessed for reliability and acceptability - Rowland Universal Dementia Assessment Screen (RUDAS) (n = 19), PEBL Corsi Blocks (Corsi) (n = 19), Story Memory Recall Test (SMRT) (n = 17) and a CogState battery (n = 18). Participants performed one to three of the tests with repeated assessment to determine test-retest reliability. Qualitative interviews were conducted and analysed based on an adapted phenomenological approach to explore test acceptability. An Indigenous Reference Group gave advice and guidance. RESULTS: Intra-class correlations (ICC) for test retest reliability ranged from r = 0.58 (CogState One Back accuracy) to 0.86 (RUDAS). Themes emerged relating to general impressions, impacts on understanding and performance, appropriateness, task preferences and suggested improvements. CONCLUSIONS: RUDAS, CogState Identification task, and SMRT showed the highest reliabilities. Overall the tests were viewed as a positive challenge and an opportunity to learn about the brain despite provoking some anxiety in the patients. Caveats for test acceptability included issues related to language, impacts of convalescence and cultural relevance.