Prevalence and Patterns of Cognitive Dysfunction in Benign MS:
PRAGUE, CZECH REPUBLIC
The combination of neuropsychological profiling and quantitative magnetic resonance imaging (MRI) for patients with benign multiple sclerosis (benign MS) provides a more reliable and comprehensive definition of their disease, and thus of their prognostic factors for the subsequent evolution of their disease, according to a study presented at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).
Benign MS is generally defined as absence of locomotor disability after 15 years or more of disease onset. However, as Monica Falautano, PhD, Co-Investigator and Psychologist, Functional Unit of Psychology, San Raffaele Scientific Institute, University Vita- Salute, Milan, Italy, said, "We feel that in patients with benign multiple sclerosis, their cognition and dysfunction in cognitive performance are underestimated… as in a recent review where they detected mild [cognitive] impairment with a patient with benign multiple sclerosis."
Dr. Falautano and colleagues therefore conducted a study with the aim of investigating the prevalence and patterns of cognitive dysfunction in a large sample of patients with benign MS, and to explore conventional and diffusion tensor (DT) MRI patterns underlying this cognitive dysfunction. This should allow potential markers to be defined for identification of patients with benign MS who have a more severe "occult" disease burden, she said.
They enrolled patients with a confirmed diagnosis of benign MS, defined as absence of locomotor disability through a disease duration of 15 years or more and accompanied by an expanded disability status scale (EDSS) no more than 3.0.
The 61 patients enrolled had a mean age of 46 years and 38% were male. They underwent extensive neurological and neuropsychological (NPS) evaluation, and conventional and DT MRI brain scans. Their mean EDSS was 1.5 at a mean disease duration of 22 years, and with a mean education level of 12 years.
Performances in the NPS evaluation tests exploring the main cognitive domains were compared between these patients and demographically and educationally matched healthy controls. These domains and tests were for: language (Token test; Phonemic fluency [VPF]; Semantic fluency), memory (Digit span; Corsi span [CS]; Short tale [ST]; Acquisition of pairs of words [APW]; Rey-Osterrieth recall), executive functions (Raven matrices; Wisconsin card sorting test), construction (Rey- Osterrieth copy [copy ROCF]; Ten-point clock test), and attention (Attentive matrices; Trail-making test [TMT]; Paced auditory serial attention test [PASAT]; Stroop test).
Following the MRI acquisition and analysis, two sets of comparisons were analysed within the benign MS patient group, based on definitions of cognitive impairment (patient test score 2 standard deviations below normal control mean = test failed) and cognitive normality (all patient test scores at or above the normal control mean).
This identified paired groups of patients who were cognitively impaired (n = 11; failure in three tests) versus cognitively unimpaired (n = 50) and cognitively normal (n = 21) versus not cognitively normal (n = 40).
The performances in individual tests across the cognitively unimpaired versus cognitively impaired comparison demonstrated significant group differences for attentive-executive functioning, verbal learning, long-term memory and visual-spatial cognition: TMT (P =.008), PASAT (P =.013), CS (P =.006), ST (P =.010), APW (P =. 003), VPF (P =.016) and copy ROCF (P =.002).
Similar differences were seen for cognitively normal versus not cognitively normal, with better performances for exploring attentive- executive functioning and verbal long-term memory: TMT (P =.013), ST (P =.001 and CS (P =.032).
When related to conventional and DT MRI findings, these different patient subgroups again showed some significant differences. For cognitively unimpaired versus cognitively impaired significant differences were seen for normal-appearing white matter (NAWM) mean diffusivity (P =.010) and its peak height (P =.001), NAWM fractional anisotropy (P =.008) and its peak height (P =.001), and grey matter mean diffusivity (P =.018).
For cognitively normal versus not cognitively normal, the only significant difference across the MRI data was for peak height of NAWM fractional anisotropy (P =.028).
These analyses indicate that despite absence of locomotor disability in patients with benign MS, the prevalence of cognitive impairment is similar to that of the general population of patients with MS (40%-65%). This finding thus confirms that criteria for identifying benign MS are misleading as it actually represents a clinical category where a significant proportion can have clinically undetected cognitive problems, according to the researchers.
Overall, these MRI findings are consistent with more severe "occult" brain tissue damage in the cognitively impaired and not cognitively normal patients with benign MS than in their respective comparative groups, suggesting that these subgroups of patients with benign MS might also differ in their medium to long-term clinical evolution.
Dr. Falautano noted, "It is also important for patients with benign multiple sclerosis to undergo neuropsychological evaluation because even if they do not present physical impairment, we can find mild or also moderate cognitive impairment, which will be important for their treatment."