Rao and co-workers (1991) demonstrated that mild cognitive impairment can appear early in MS and that it does not correlate with overall neurological impairment. They identified a series of tests that were sensitive to the cognitive changes typically seen early in MS patients and published them as the BRBN (Rao et al., 1990). The BRBN consisted of the five standard tests of memory and attention, the Selective Reminding, 10/36 Spatial Recall, Symbol Digits Modalities, Paced Auditory Serial Addition, and Word List Generation tests.
Because of anecdotal reports of improved memory and concentration while on potassium channel blockers, two studies examined the effects of potassium channel blockers on cognitive dysfunction in patients with MS using the BRBN. Smits and co-workers (1994) reported a randomized, double blind, placebo-controlled, crossover design trial examining the effects of oral AP given over a 14-day period. They found trends toward improvement in some measures but no statistically significant changes. Bever and co-workers (1997) included the BRBN in their evaluation of 36 patients treated with DAP in a randomized, placebo-controlled, double-blind, crossover design trial. No significant differences were found. Despite anecdotal reports of improved cognition in patients receiving AP and DAP, these well-designed trials using a neuropsychological testing bat tery designed to be sensitive to the deficits typically seen in early MS patients found no improvement.
Rossini and co-workers (2001) reported a study of the effects of AP on neurocognitive dysfunction using a larger, more generalized battery of tests. A total of 60 primary and secondary progressive patients with MS were randomized in a double-blind, placebo-controlled, crossover trial of oral AP using 6-month treatment periods. A total of 49 patients completed the study. The testing battery included tests for sustained attention (the Auditory Attention test), short-term memory (the Forward Digit and Corsi's Block Span tests), long-term memory (the 15' Delayed Recall of Rey's 15-Words List and the 15' Delayed Recall of Rey's Figure A tests), visual perception (Benton's Line Orientation test), language (Token test), executive function (Wisconsin Card Sorting test), general intelligence (Raven's Progressive Maticies test), and depression (Hamilton's scale). Neither the study group as a whole nor a subgroup analysis based on serum AP levels showed any treatment-related changes. Studies to date fail to demonstrate any effect of AP or DAP on cognition.
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