Cognitive impairment in multiple sclerosis: clinical management, MRI, and therapeutic avenues

Abstract

Multiple sclerosis is a chronic, demyelinating disease of the CNS. Cognitive impairment is a sometimes neglected, yet common, sign and symptom with a profound effect on instrumental activities of daily living. The prevalence of cognitive impairment in multiple sclerosis varies across the lifespan and might be difficult to distinguish from other causes in older age. MRI studies show that widespread changes to brain networks contribute to cognitive dysfunction, and grey matter atrophy is an early sign of potential future cognitive decline. Neuropsychological research suggests that cognitive processing speed and episodic memory are the most frequently affected cognitive domains. Narrowing evaluation to these core areas permits brief, routine assessment in the clinical setting. Owing to its brevity, reliability, and sensitivity, the Symbol Digit Modalities Test, or its computer-based analogues, can be used to monitor episodes of acute disease activity. The Symbol Digit Modalities Test can also be used in clinical trials, and data increasingly show that cognitive processing speed and memory are amenable to cognitive training interventions.

Figure 1

SDMT decline and recovery curves in patients with cognitive relapse Change from baseline in the difference between relapsing (defined by clinical diagnosis of gadolinium enhancement on MRI) patients and stable patients in raw SDMT score. For each study, the mean of the stable control group is subtracted from the mean SDMT score of the relapsing group. The relapsing and stable groups are generally well matched at baseline with the difference in scores ranging from −0·7 to 0·6. In each study, the relapsing group recovers after the relapse timepoint, to varying degrees, seldom returning to a difference score of 0. SDMT=Symbol Digit Modalities Test.

Figure 2

Brain MRI of a 53-year-old man with relapsing-remitting multiple sclerosis Contrast axial brain MRI scan images obtained from the patient (described in panel 3) during and after relapse with documented cognitive impairment. MRI was obtained on a 3·0T GE Signa Excite HD 12 Twin-Speed scanner (GE, Milwaukee, WI, USA). At both timepoints, T1-weighted images were acquired with a single-dose intravenous bolus of 0·1 mmol/kg gadolinium-pentetic acid 5 min after injection. The lesions that appear by use of this method represent a breakdown of the blood–brain barrier, allowing myelin-reactive T cells to enter the CNS and cause a cascade of inflammatory changes that lead to oedema, demyelination, and axonal loss. During the relapse timepoint, several gadolinium-enhancing MRI brain lesions of 0·8 cm³ or greater volume were present (arrows). In total, 13 lesions were identified but not all are visible in these sections. The gadolinium-enhancing lesions were no longer observable at the recovery timepoint, indicating a recovery of the blood–brain barrier, although some tissue damage (not shown) might persist.