Clinical and MRI characterization of MS patients with a pure and severe cognitive onset

• We described a rare form of MS with initial severe and isolated cognitive deficit.
• The extended cognitive impairment remained predominant during the whole disease.
• Main associated symptoms involved mood, pseudo-bulbar affect, bladder and gait.
• Brain MRI showed severe and quickly progressive atrophy.
• There was an unusual diagnosis delay for these patients.

Background and objectiveCognitive and behavioural symptoms are common in multiple sclerosis (MS), but they are rarely the inaugural and predominant manifestation of the disease. Our objective is to characterize the clinical and radiological features of cognitive-multiple sclerosis (cog-MS), defined as MS subjects who entered into the disease with cognitive symptoms, which subsequently remain the predominant manifestation.MethodsWe describe the disease course, and clinical and radiological features of 18 subjects with a cognitive form of MS.ResultsMemory loss and behavioural changes were the primary symptoms at disease onset. They remained prominent and led to severe cognitive impairment during disease course. The main associated manifestations were depression, pathological laughing and/or crying, urinary incontinence and gait disturbance suggestive of high-level gait disorder. Motor, sensory or cerebellar abnormalities were uncommon. During disease course, superimposed neurological relapses occurred in 61% of cases. Brain MRI revealed multiple periventricular lesions that were extensive and confluent in half of cases, and a severe atrophy measured as an increase in the third ventricular width compared to age-matched healthy controls. Gadolinium-enhancing lesions were common (72%). The mean diagnosis delay from disease onset was 2 years. A principal component analysis on the neuropsychological results revealed that verbal memory assessment is complementary to global cognitive functioning evaluation in these patients with severe cognitive deficit. Verbal memory deficit was associated with high EDSS.Conclusionscog-MS patients might represent a challenging diagnosis, which needs to be individualized for an early management.