Brainstem lesions in clinically isolated syndromes M. Tintore, MD A. Rovira, MD G. Arrambide, MD R. Mitjana, MD J. Río, MD C. Auger, MD C. Nos, MD M.C. Edo, MD J. Castillo ´, MD A. Horga, MD F. Perez-Miralles, MD E. Huerga, RT M. Comabella, MD J. Sastre-Garriga, MD X. Montalban, MD ABSTRACT Background: Number of baseline lesions has been shown to predict future attacks and disability in clinically isolated syndromes (CIS). Objective: To investigate the role of baseline infratentorial lesions in long-term prognosis. Methods: Subjects were included in a prospective cohort of patients with CIS. Patients under- went brain MRI within 3 months after CIS onset. Number and location of lesions at baseline were prospectively studied. Retrospective scan analysis was conducted to specifically look at number and location of infratentorial lesions. We analyzed the time to a second attack and to reach EDSS 3.0. Results: We included 246 patients with CIS followed for a median of 7.7 years. Patients with infratentorial lesions had both a higher risk of conversion (71.4% vs 29.6%; hazard ratio [HR] 3.3; 95% confidence interval [CI] 2.2–4.8; p  0.001) and of developing disability (32.5% vs 12.4%; HR 2.4; 95% CI 1.3–4.3; p = 0.003). Presence of at least one cerebellar lesion was associated with an increased risk of conversion (HR 2.4; 95% CI 1.3–4.5; p = 0.007). Presence of at least one brainstem lesion increased both the risk of conversion (HR 2.9; 95% CI 1.7–5.0; p  0.001) and disability (HR 2.5; 95% CI 1.1–5.4; p = 0.026). Broken down into number of lesions, the presence of infratentorial lesions increased both the risk of conversion (83% vs 61%) (HR 22.3; 95% CI 9.7–51.1; p  0.001) and of reaching EDSS 3.0 (40% vs 19%) (HR 3.2; 95% CI 1.3–7.4; p = 0.008) only in patients with 9 or more lesions. Conclusions: Presence of infratentorial lesions increases the risk for disability. Brainstem rather than cerebellar lesions may be responsible for poor prognosis. Neurology ® 2010;75:1933–1938 GLOSSARY CDMS = clinically definite multiple sclerosis; CI = confidence interval; CIS = clinically isolated syndrome; EDSS = Expanded Disability Status Scale; HR = hazard ratio; MS = multiple sclerosis. Multiple sclerosis (MS) usually presents with a clinically isolated syndrome (CIS), typically optic neuritis, internuclear ophthalmoplegia, or partial myelitis. Once a first attack has oc- curred, it is important to estimate the future risk of developing MS and disability. Clinical features, multimodal evoked potentials, biologic markers, and MRI findings have been associ- ated with the risk of conversion or development of disability. MRI, nonetheless, has been shown to be the most informative predictive marker. 1-8 The number of lesions at baseline is related to the time to reach clinically definite MS (CDMS). Hence, patients with fewer lesions require longer times until they reach conversion rates similar to patients with a higher number of lesions. Number of lesions (0, 1–9, 10 or more) or number of Barkhof criteria (0, 1–2, 3– 4) allow us to identify patients with low, medium, and high risk to present a second attack. 9 As for develop- ment of disability, the number of baseline lesions and the number of Barkhof criteria correlate with Expanded Disability Status Scale (EDSS) score at year 5. 9 Moreover, a recent study has shown that lesion volume and its change during the first 5 years are correlated with disability after 20 years. 10 From CENTRE: Multiple Sclerosis Centre of Catalonia, Clinical Neuroimmunology Unit (M.T., G.A., J.R., C.N., M.C.E., J.C., A.H., F.P.-M., M.C., J.S.-G., X.M.), and Magnetic Resonance Unit (IDI) and Department of Radiology (A.R., R.M., C.A., E.H.), Hospital Universitari Vall d’Hebron, Universitat Auto `noma de Barcelona, Barcelona, Spain. Study funding: Supported in part by the Fondo de Investigacio ´n Sanitaria (FIS PI08/0788). Disclosure: Author disclosures are provided at the end of the article. Address correspondence and reprint requests to Dr. Mar Tintore, Unitat de Neuroimmunologia Clinica (UNIC), Edif. Escola d’infermeria planta 2, Hospital Universitari Vall d’Hebron, Pg Vall d’Hebron 119-129, 08035 Barcelona, Spain mtintore@vhebron.net Supplemental data at www.neurology.org Copyright © 2010 by AAN Enterprises, Inc. 1933