Clinical Neurology and Neurosurgery 115 (2013) 1032–1035 Contents lists available at SciVerse ScienceDirect Clinical Neurology and Neurosurgery j o ur nal hom epage: www.elsevier.com/locate/clineuro Cognitive impairment and optic nerve axonal loss in patients with clinically isolated syndrome C.F. Anhoque a , L. Biccas-Neto b , S.C.A. Domingues c , A.L. Teixeira a,c , R.B. Domingues a,d,∗ a Neuroscience Postgraduation Program, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil b Surgery Department, Santa Casa, School of Health Sciences, Vitória, ES, Brazil c Department of Internal Medicine, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil d Department of Pathology and Internal Medicine, Santa Casa School of Health Sciences, Vitória, ES, Brazil a r t i c l e i n f o Article history: Received 22 May 2012 Received in revised form 16 August 2012 Accepted 25 October 2012 Available online 20 November 2012 Keywords: Cognition Clinically isolated syndrome Neuropsychological tests Optic nerve Axonal loss Optical coherence tomography a b s t r a c t Objective: To investigate cognitive impairment, to assess optical nerve axonal loss, and to determinate whether there is correlation between optical nerve axonal loss and cognition impairment in Clinically Isolated Syndrome (CIS). Methods: Fifteen CIS patients and 15 controls were submitted to Wechsler memory scale, Rey Auditory Verbal Learning, Rey Complex Figure, Paced Auditory Serial Addition, Digit Span, verbal fluency, stroop color, D2, and Digit Symbol tests. CIS patients were evaluated by optical coherence tomography (OCT) (23 eyes). Results: CIS patients had worse performance in Paced Auditory Serial Addition Test (PASAT) 2 seconds (P = 0.009) and fluency tests (P = 0.0038). Optical nerve axonal loss was found more frequently in eyes with previous optic neuritis (ON) (85.7%) than in those without previous ON (21.7%) (P = 0.0146). There were no significant correlations between optical nerve axonal loss and cognitive findings. Conclusions: CIS patients had worse cognitive performance than controls. OCT can detect axonal loss resulting from optical neuritis and subclinical axonal loss in eyes without previous optical neuritis. Optical nerve axonal loss was not correlated with cognition. © 2012 Elsevier B.V. All rights reserved. 1. Introduction Cognitive impairment is present in 40–65% of patients with mul- tiple sclerosis (MS) [1] and it is correlated with the number and localization of the demyelinating plaques, axonal loss, and brain atrophy [2]. Clinically isolated syndrome (CIS) is defined as the first episode of a demyelinating and inflammatory disease of the cen- tral nervous system (CNS) and most patients with CIS will convert to multiple sclerosis (MS) [3,4]. Patients with the first demyeli- nating episode may already be diagnosed as having MS if both gadolinium-enhancing and nonenhancing lesions on the baseline magnetic resonance imaging (MRI) are found [5]. Some studies have shown that cognitive deficits may be detected in patients with CIS [1,6–10]. Progressive brain atrophy is a well-known feature of MS and is considered as a marker of irreversible tissue damage of both ∗ Corresponding author at: Rua Prof. Almeida Cousin, 125, sala 1310, Bairro Enseada do Suá, CEP 29.055-565, Vitória, ES, Brazil. Tel.: +55 27 3345 7056; fax: +55 27 3315 4620. E-mail address: contato@renandomingues.med.br (R.B. Domingues). gray matter and white matter [11]. Brain damage and brain atro- phy reflect axonal loss and are correlated with cognitive outcome in multiple sclerosis [12,13]. Recently, measures of retinal nerve fiber layer thickness (RNFL) by optical coherence tomography (OCT) showed to be a potentially reliable predictor outcome in MS and optic neuritis [14–16]. Some studies have demonstrated correlation between optical nerve atrophy measured by RNFL and the degree of brain atrophy in patients with MS [16]. However, there are still concerns about the use of OCT for measuring global axonal injury in MS [18]. Taking into account the correlation between cognitive impair- ment and brain atrophy and the correlation between brain atrophy and optical nerve atrophy it is reasonable to hypothesize a correla- tion between cognitive decline and optical nerve atrophy measured by OCT. In fact, a correlation between optical nerve atrophy mea- sured by OCT and cognitive impairment was shown in patients with MS [19]. However, it is not known whether such correlation occurs at all stages of disease and if it can already be observed in patients with CIS. The aim of the present study was to investigate the pres- ence and frequency of cognitive impairment, to assess optical nerve atrophy with OCT, and to assess the correlation between optical nerve atrophy and cognitive deficits in patients with CIS. 0303-8467/$ – see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.clineuro.2012.10.025