We previously showed that a fully automated voice recognition analog of the Symbol Digit Modalities Test (VR-SDMT) is sensitive in detecting processing speed deficits in people with multiple sclerosis (pwMS). We subsequently developed a French language version and administered it to 49 French-Canadian pwMS and 29 matched healthy control (HC) subjects. Significant correlations between the VR-SDMT and traditional oral SDMT were found in the MS (r = −0.716, p < 0.001) and HC (r = −0.623, p < 0.001) groups. These findings in French replicate our previous findings and confirm the utility of voice recognition software in assessing cognition in pwMS.

Objective: The Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) is a consensus-based collection of neuropsychological tests that evaluate cognitive functioning in individuals with multiple sclerosis (MS). The tests are typically scored using each respective published test manual, leaving the examiner to make interpretations from norms derived from different American populations. Given demographic differences, this may lead to misinterpretation of findings in Canadians. Our goal was to establish both discrete and regression-based normative data for the MACFIMS based on a largely co-normed Canadian population to allow for improved psychometric interpretation. Methods: MACFIMS data sets were aggregated from across three different Canadian cities (Ottawa, Toronto, and London), yielding a total of 330 healthy control participants from four different studies evaluating cognition in individuals with MS. Given the variety of contributing studies, there was variability in terms of the number of participants completing each measure. Results: Both age-based discrete normative data and demographically adjusted (sex, age, and education) regression-based formulae were established. The demographic variables varied in their contribution to each MACFIMS test in the regression models, predicting 0 to 18% of the variance. Conclusions: Provision of these regression-based formulae will allow for more accurate interpretation of Canadian-derived MACFIMS scores by allowing clinicians to correct for all relevant demographic variables simultaneously, leading to improved clinical decision making for individuals with multiple sclerosis.

Objective: In multiple sclerosis (MS), magnetic resonance imaging (MRI) predictors of cognitive impairment are based on sophisticated computer-generated analyses that are difficult to apply in clinical settings. This study investigated the clinical usefulness of a new visual rating scale, the Cholinergic Pathways Hyperintensities Scale (CHIPS), in detecting cognitive dysfunction.

Methods: Forty clinically definite MS patients underwent a brain MRI. Based on the CHIPS, cholinergic pathway hyperintensities were rated in 10 regions on four axial slices. Computerized hyperintense lesion volumes were also obtained. For cognitive testing, The Neuropsychological Screening Battery for Multiple Sclerosis was used. “Low” and “High” lesion score groups were computed based on the mean of the total CHIPS score. Optimal sensitivity and specificity of the total CHIPS score in detecting cognitive impairment were determined using a receiver operator characteristic curve.

Results: Despite a similar demographic profile, subjects with a “High” lesion score performed significantly worse than the “Low” lesion score group on verbal (P=.007) and visuospatial (P=.02) memory, and on a global index of cognitive functioning (P=.001). Optimal sensitivity (82%) and specificity (83%) were reached with a threshold total CHIPS score of 18 points. Total CHIPS score and total hyperintense lesion load were correlated (σ=0.82, P<.0001).

Conclusion: CHIPS is helpful in clinically predicting cognitive impairment in MS.

Multiple sclerosis (MS) is the most common cause of neurological disability in young and middle-aged adults. Although Charcot noted behavioral changes associated with MS, nearly a century would elapse before researchers began defining their full extent and severity. Broadly speaking, abnormalities may be divided into those of mood and cognition. Many patients are afflicted with both and it is essential that clinicians are not only aware of this but understand how to detect problems and provide treatment.

The lifetime prevalence of major depression in MS patients approaches 50%. As Scott B. Patten, MD, and colleagues note, these data came from specialist clinics with the potential for ascertainment bias. Shifting their inquiry into a large community-based sample, they report that the rates of mood disorder remain elevated largely in younger MS patients. While it is partly reassuring to find that aging comes with at least one benefit, the gist of this study is to reinforce the message that clinically significant depression is a problem for MS patients. Not only does it adversely affect quality of life and lead to increased suicidal thinking, it exerts more subtle deleterious effects as Peter A. Arnett, PhD, reveals. In a longitudinal study exploring the relationship between depression and cognition, Arnett reports that MS patients with prominent evaluative symptoms of depression (ie, feelings of inferiority, failure) have greater difficulty with cognitive tasks that encompass information processing speed and executive function linked to working memory. A preoccupation with negative thoughts may reduce the cognitive capacity necessary for aspects of attention and working memory.

These data complement the review article of Ralph H.B. Benedict, PhD, ABPP-CN, that focuses on methods of detecting cognitive dysfunction in MS. As with mood disorders, impaired cognition has been linked to difficulties with work, relationships, and, in more extreme cases, basic activities of daily living. Usually, the more subtle pattern of deficits associated with demyelination differ from those seen in cortical-type dementias and will be missed should clinicians rely on screening instruments like the Mini-Mental State Examination. At the same time, the method of choice for eliciting deficits, namely neuropsychological testing is expensive and frequently not readily available. This has meant that alternative instruments, like the Multiple Sclerosis Neuropsychological Screening Questionnaire, assume an added prominence. With good sensitivity, specificity, and ease of administration this informant based scale makes a useful addendum to the neurological examination. It is in the same light that the magnetic resonance imaging (MRI) rating scale by Laury Chamelian, MD, FRCPC, and colleagues should be viewed.

DNA methylation differences between identical twins could account for phenotypic twin discordance of behavioral traits and diseases. High throughput epigenomic microarray profiling can be a strategy of choice for identification of epigenetic differences in phenotypically different monozygotic (MZ) twins. Epigenomic profiling of a pair of MZ twins with quantified measures of psychometric discordance identified several DNA methylation differences, some of which may have developmental and behavioral implications and are consistent with the contrasting psychometric profiles of the twins. In particular, differential methylation of CpG islands proximal to the homeobox DLX1 gene could modulate stress responses and risk taking behavior, and deserve further attention as a potential marker of aversion to danger. The epigenetic difference detected at DLX1 of ∼1.2 fold change was used to evaluate experimental design issues such as the required numbers of technical replicates. It also enabled us to estimate the power this technique would have to detect a functionally relevant epigenetic difference given a range of 1 to 50 twin pairs. We found that use of epigenomic microarray profiling in a relatively small number (15–25) of phenotypically discordant twin pairs has sufficient power to detect 1.2 fold epigenetic changes.