Influence of cigarette smoking on white matter in patients with clinically isolated syndrome as detected by diffusion tensor imaging.

Clinically isolated syndrome (CIS), an inflammatory demyelinating disorder of the central nervous system, is the first clinical episode with features predictive of multiple sclerosis (MS) (1). Many environmental risk factors for conversion from CIS to MS were shown in recent studies (1, 2). Among these, cigarette smoking was shown to increase the risk of developing MS even in passive smokers (3), worsen clinical disability, and exacerbate disease progression (4). Diffusion tensor imaging (DTI) gives the opportunity to evaluate the tissue integrity, mainly the white matter (WM). Through changes in metrics such as fractional anisotropy (FA) and mean diffusivity (MD), DTI enables the assessment of axonal organization and myelin attenuation in addition to the WM lesions evaluated by conventional magnetic resonance imaging (MRI) sequences (5). The brains of MS patients have demonstrated that an increase in MD and a decrease in FA values were far beyond fluid attenuation inversion recovery (FLAIR) hyperintense lesions, commonly used as a clinical parameter of MS (6, 7). Brain parenchyma with no apparent lesion, namely, the normal-appearing white matter (NAWM), has drawn much attention due to the presence of not only histopathologic and radiologic abnormalities but also a close association with clinical disability and disease progression (8). Changes in the NAWM may also be responsible for the clinicoradiologic discrepancy observed in many patients (6). In addition, several MRI studies have shown significantly altered FA measures in specific brain regions in healthy smoker individuals (9, 10). Although a number of studies have investigated the impact of smoking on patients with MS (4, 11), to the best of our knowledge, no study has studied the influence of smoking on the WM in patients with CIS using DTI. In this study we sought to determine the effects of smoking on NAWM, lesions, and perilesional WM of patients with CIS. The secondary objective was to examine whether diffusion tensor changes relate to the duration of disease, clinical disability and degree of smoking exposure.