SWAN-Venule: An Optimized MRI Technique to Detect the Central Vein Sign in MS Plaques.

BACKGROUND AND PURPOSE: Multiple sclerosis lesions develop around small veins that are radiologically described as the so-called central vein sign. With 7T MR imaging and magnetic susceptibility-based sequences, the central vein sign has been observed in 80%-100% of MS lesions in patients' brains. However, a lower proportion ∼50% has been reported at 3T using susceptibility-weighted angiography (SWAN). Our aim was to assess a modified version of SWAN optimized at 3T for sensitive detection of the central vein sign. MATERIALS AND METHODS: Thirty subjects with MS were scanned on a 3T clinical MR imaging system. 3D T2-weighted FLAIR and optimized 3D SWAN called SWAN-venule, were acquired after injection of a gadolinium-based contrast agent. Patients showing >3 focal white matter lesions were included. The central vein sign was recorded by 2 trained raters on SWAN-venule images in the supratentorial brain. RESULTS: Twenty patients showing >3 white matter lesions were included. A total of 380 white matter lesions (135 periventricular, 144 deep white matter, and 101 juxtacortical) seen on both FLAIR and SWAN-venule images were analyzed. Overall, the central vein sign was detected in 86% of the white matter lesions (periventricular, 89%; deep white matter, 95%; and juxtacortical, 78%). CONCLUSIONS: The SWAN-venule technique is an optimized MR imaging sequence for highly sensitive detection of the central vein sign in MS brain lesions. This work will facilitate the validation and integration of the central vein sign to increase the diagnostic certainty of MS and further prevent misdiagnosis in clinical practice.

Disease activity impacts disability progression in primary progressive multiple sclerosis.

BACKGROUND: Although solid information on the natural history of primary progressive multiple sclerosis (PPMS) is available, evidence regarding impact of disease activity on PPMS progression remains controversial. OBJECTIVE: To describe the clinical characteristics, presence or absence of MRI activity, and natural history of a PPMS cohort from two referral centers in Argentina and assess whether clinical and/or radiological disease activity correlated with disability worsening. METHODS: Retrospective study conducted at two MS clinics in Buenos Aires, Argentina, through comparative analysis of patients with and without evidence of disease activity. RESULTS: Clinical and/or radiologic activity was presented in 56 (31%) of 178 patients. When stratified by age at onset, we found that for every 10 years of increase in age at onset, risk of reaching EDSS scores of 4 and 6 increased by 26% and 31%, respectively (EDSS 4: HR 1.26, CI 95%: 1.06-1.50; EDSS 6: HR 1.31, CI 95%: 1.06-1.62). Patients who presented clinical exacerbations reached EDSS scores of 6, 7 and 8 faster than those without associated exacerbations (p = 0.009, p = 0.016 and p = 0.001, respectively). Likewise, patients who presented gadolinium-enhancing lesions during the course of disease reached EDSS scores of 7 earlier (p = 0.002). CONCLUSION: Older age at onset and presence of clinical and/or radiological disease activity correlated with accelerated disability progression in this cohort of PPMS patients.

Multiple sclerosis and environmental factors: the role of vitamin D, parasites, and Epstein-Barr virus infection.

Pathogenic mechanisms underlying multiple sclerosis development have yet to be clearly identified, but considerable evidence indicates that autoimmunity plays an important role in the etiology of the disease. It is generally accepted that autoimmune diseases like MS arise from complex interactions between genetic susceptibility and environmental factors. Although environmental factors unequivocally influencing MS development have yet to be established, accumulating evidence singles out several candidates, including sunlight-UV exposure or vitamin D deficiency, viral infections, hygiene, and cigarette smoking. Vitamin D deficiency has been associated with different autoimmune diseases. Several investigations indicate 125 (OH)2 vitamin D plays a critical role in shaping T-cell response and inducing T cells with immunosuppressive properties. Likewise, helminth infections represent another potential environmental factor exerting immunomodulatory properties. Both epidemiological and experimental data provide evidence to support autoimmune down-regulation secondary to parasite infections in patients with MS, through regulatory T- and B-cell action, with effects extending beyond simple response to an infectious agent. Finally, different epidemiological studies have demonstrated that Epstein-Barr virus infection confers added risk of developing MS. Proposed mechanisms responsible for this association include activation and expansion of self-reactive T and B cells, lower threshold for self-tolerance breakdown, and enhanced autoreactive B-cell survival, all to be discussed in this review. Understanding environmental factors influencing propensity to MS will lead to new and more effective approaches to prevent and treat the disease.