Faculty Bibliography

The epidemiology of multiple sclerosis (MS) includes a consideration of genetic and environmental factors. Comparative studies of different populations have revealed prevalence and incidence rates that vary with geography and ethnicity. With a prevalence ranging from 2 per 100,000 in Japan to greater than 100 per 100,000 in Northern Europe and North America, the burden of MS is similarly unevenly influenced by longevity and comorbid disorders. Well-powered genome-wide association studies have investigated the genetic substrate of MS, providing insight into autoimmune mechanisms involved in the etiopathogenesis of MS and elucidating possible avenues of biological treatment.

OBJECTIVES: Not all patients referred for evaluation of multiple sclerosis (MS) meet criteria required for MS or related entities. Identification of markers to exclude demyelinating disease may help detect patients whose presenting symptoms are inconsistent with MS. In this study, we evaluate whether patients who present a self-prepared list of symptoms during an initial visit are less likely to have demyelinating disease and whether this action, which we term the "list sign," may help exclude demyelinating disease. METHODS: Using chart review, 300 consecutive new patients who presented for evaluation to a neurologist at a tertiary MS referral center were identified retrospectively. Patients were defined as having demyelinating disease if diagnosed with MS or a related demyelinating condition. RESULTS: Of the 233 enrolled subjects, 157 were diagnosed with demyelinating disease and 74 did not meet criteria for demyelinating disease. Fifteen (8.4%) subjects had a positive list sign, of which 1 patient had demyelinating disease. The 15 subjects described a mean of 12.07 symptoms, and 8 of these patients met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for somatic symptom disorder. The specificity and positive predictive value of the list sign for non-demyelinating disease were 0.99 (95% confidence interval (CI) 0.96-0.99) and 0.93 (95% CI 0.66-0.99), respectively. CONCLUSION: A positive list sign may be useful to exclude demyelinating disease and to guide diagnostic evaluations for other conditions. Patients with a positive list sign also have a high incidence of somatic symptom disorder.

Previous studies comparing phase sensitive inversion recovery (PSIR) to double inversion recovery (DIR) have demonstrated that use of PSIR improves cross-sectional in vivo detection of cortical lesions (CL) in multiple sclerosis. We studied the utility of PSIR in detection/characterization of accrual of CL over time in a 1-year longitudinal study in primary progressive multiple sclerosis (PPMS) compared to DIR. PSIR and DIR images were acquired with 3T magnetic resonance imaging (MRI) in 25 patients with PPMS and 19 healthy controls at baseline, and after 1 year in 20 patients with PPMS. CL were classified as intracortical, leucocortical or juxtacortical. Lesion counts and volumes were calculated for both time points from both sequences and compared. Correlations with measures of physical and cognitive disability were determined as well as new CL counts and volumes. Compared to DIR, PSIR led to detection of a higher number of CL involving a larger proportion of patients with PPMS both cross-sectionally (p = 0.006, 88%) and longitudinally (p = 0.007, 95%), and led to the reclassification of a third of CL seen on DIR at each time point. Interestingly, PSIR was more sensitive to new CL accumulation over time compared to DIR. PSIR is a promising technique to monitor cortical damage and disease progression in patients with PPMS over a short-term follow-up.