ObjectivesWhether transcranal sonography (TCS) depicted third ventricular enlargement as a sign of brain atrophy is predictive for neuropsychological deficits in mildly affected patients with multiple sclerosis (MS).DesignCross-sectional study of a cohort of mildly diseased patients with MS.SettingNeurological MS outpatient clinic at a large teaching hospital in central Europe.ParticipantsFifty-four patients with MS (16 men, 38 women, mean age 40±10 years, mean disease duration 6±5 years; mean Expanded Disability Status Scale 2±1.3) and 33 healthy controls (12 men, 21 women; 38±11 years) underwent clinical examination, an assessment of the third ventricle width by means of TCS and the Brief Repeatable Battery of Neuropsychological tests for MS, the 25-Feet Foot Walk test, the 9-Hole PEG test, the Beck Depression Inventory and a quantitative fatigue assessment. Statistical analysis was performed with univariate correlation and thereafter by stepwise regression analysis.ResultsPatients’ mean third ventricular width (3.9±1.6 mm) was significantly wider compared to controls (3.4±0.8 mm). Using stepwise regression analysis models with age, MS duration, third ventricle width and quantitative fatigue assessment as baseline variables, an increasing third ventricle width significantly correlated with the target variables worsening of motor deficits (p<0.002), worsening of verbal recall (p<0.04) and of visual spatial recall (p<0.005). Severity of depression and of fatigue was unrelated to third ventricular width.ConclusionsIn this cohort of patients with MS with mild disease, third ventricular enlargement was indicative for motor deficits and cognitive impairment, even after considering fatigue as a relevant comorbidity. Third ventricular enlargement by means of TCS seems to be a useful, clinically meaningful parameter to stage patients’ disease severity. Follow-up studies must show whether an intraindividual future third ventricular increase indeed signals larger cognitive impairment.