Regional cortical thinning in multiple sclerosis and its relation with cognitive impairment: A multicenter study.

OBJECTIVES: The objectives of this paper are to compare in a multicenter setting patterns of regional cortical thickness in patients with relapsing-remitting multiple sclerosis (RRMS) and cognitive impairment (CI) and those cognitively preserved (CP), and explore the relationship between cortical thinning and cognitive performance. METHODS: T1-weighted isotropic brain scans were collected at 3T from seven European centers in 60 RRMS patients and 65 healthy controls (HCs). Patients underwent clinical and neuropsychological examinations. Cortical thickness (CTh) measures were calculated using FreeSurfer (failing in four) and both lobar and vertex-based general linear model (GLM) analyses were compared between study groups. RESULTS: Twenty (36%) MS patients were classified as CI. Mean global CTh was smaller in RRMS patients compared to HCs (left 2.43 vs. 2.53 mm, right 2.44 vs. 2.54 mm, p < 0.001). Multivariate GLM regional analysis showed significantly more temporal thinning in CI compared to CP patients. Verbal memory scores correlated to regional cortical thinning in the insula whereas visual memory scores correlated to parietal thinning. CONCLUSIONS: This multicenter study showed mild global cortical thinning in RRMS. The extent of thinning is less pronounced than previously reported. Only subtle regional differences between CI and CP patients were observed, some of which related to specific cognitive domains.

Non-lesional white matter changes in pediatric multiple sclerosis and monophasic demyelinating disorders.

OBJECTIVE: To analyze diffusion tensor imaging (DTI) derived metrics between patients with childhood onset multiple sclerosis (MS), monophasic demyelinating illnesses, and healthy controls. BACKGROUND: Monophasic demyelinating illnesses can be indistinguishable clinically and radiologically, utilizing standard MRI studies. DTI studies in adults implicate the involvement of normal-appearing white matter (NAWM) in MS. METHODS: Subjects with DTI studies (15 directions, 1.5 Tesla (GE), 3x3x3 mm, interpolated to 1.5x1.5x3 mm) were retrospectively identified. We studied three groups: childhood onset MS (n=18), monophasic illness (eight with acute disseminated encephalomyelitis (ADEM), seven with clinically isolated syndrome (CIS)) and age-matched controls. DTI had been obtained within one month of symptom onset for patients with ADEM and within a median of 20 months for the MS group. DTI measures were determined using a semi-automated method from standardized regions of interest (ROI) containing central fibers of the corpus callosum genu and internal capsule. RESULTS: The MS group had significantly lower fractional anisotropy (FA) values compared to controls (p<0.001), with increased radial diffusivity (RD) and decreased axial diffusivity (AD). In the monophasic group FA was smaller than the controls (p=0.01) with increased RD and no difference in AD. CONCLUSIONS: This retrospective analysis provides evidence that NAWM is affected in pediatric MS and monophasic demyelinating disease, with a potentially novel pattern demonstrating reduced AD in pediatric MS. Further larger scale confirmatory studies are needed to address whether the demonstrated DTI changes could be used as a biomarker in pediatric patients presenting with an initial demyelinating event.

Dark Rims: Novel Sequence Enhances Diagnostic Specificity in Multiple Sclerosis.

BACKGROUND AND PURPOSE: The 2010 McDonald criteria are designed to sensitively detect MS; however, the low specificity of these criteria can occasionally lead to the misdiagnosis of MS. The purpose of this study was to determine whether a novel double inversion recovery MR imaging technique has the potential to increase the specificity of diagnostic criteria distinguishing MS from non-MS white matter lesions. MATERIALS AND METHODS: This was a cross-sectional observational study. MR imaging data were acquired between 2011 and 2016. A novel double inversion recovery sequence that suppresses CSF and GM signal was used (GM-double inversion recovery). We compared WM lesions in a group of patients with multiple sclerosis and in a second group of positive controls with white matter lesions who did not have a diagnosis of MS. The presence of a rim on the GM-double inversion recovery MR imaging sequence was combined with the 2001 and 2010 McDonald disseminated-in-space criteria. Multiple MR imaging markers, including lesion location, size, and the presence of a rim, were compared between groups as well as a quantitative measure of lesion T1 hypointensity. RESULTS: MR images from 107 patients with relapsing-remitting MS (median age, 32 years) and 36 positive control (median age, 39 years) subjects were analyzed. No significant differences were found in age and sex. In patients with MS, 1120/3211 lesions (35%) had a rim on GM-double inversion recovery; the positive control group had only 9/893 rim lesions (1%). Rims were associated with a decrease in the lesion T1 ratio. Using the 2010 MR imaging criteria plus the presence of rims on GM-double inversion recovery, we achieved 78% and 97% specificity in subjects with ≥1 and ≥2 rim lesions, respectively. CONCLUSIONS: The addition of a novel GM-double inversion recovery technique enhanced specificity for diagnosing MS compared with established MR imaging criteria.

Evaluating the association of allergies with multiple sclerosis susceptibility risk and disease activity in a pediatric population.

BACKGROUND: Multiple sclerosis (MS) and allergies are both considered to be related to imbalanced Th1 and Th2 immune responses. Previous studies evaluating the relationship between MS and allergies provide conflicting results. OBJECTIVE: To assess allergies and asthma as risk factors for MS and as predictors of MS relapses in a pediatric cohort. METHODS: The environment and genetic risk factors for pediatric MS study is a national case-control project with 16 participating US sites. An environmental questionnaire is used that includes history of allergies in the first five years of life. Case-control data are entered in the pediatric MS Network database and cases at 12 of the 16 sites enter relapse data prospectively. Annualized relapse rate was calculated for patients with follow-up and adjusted for age at disease onset, gender, race, ethnicity, and use of disease-modifying therapy (DMT). RESULTS: We included 271 cases (mean age at disease onset of 15.7years and 62% female) and 418 controls. Relapse data were available for 193 cases. There was no difference in prevalence of allergies or asthma between cases and controls. Patients with food allergies had fewer relapses compared to patients without food allergies (0.14 vs 0.48, p=0.01). CONCLUSIONS: While allergies and asthma are not associated with pediatric MS, cases with food allergies have fewer relapses compared to those without food allergies.

The spectrum of neuromyelitis optica (NMO) in childhood.

The evaluation of inflammatory central nervous system disorders in childhood with predominant involvement of the optic nerves and spinal cord has been greatly enhanced over the last decade with identification of a group of disorders unified by the detection of neuromyelitis optica (NMO)-IgG, an antibody targeting the central nervous system-predominant water channel aquaporin-4. Clinical syndromes are predominated by the relapsing form of NMO but also include encephalopathic variants that can mimic acute disseminated encephalomyelitis. Maintenance immunotherapy is used to prevent relapses in NMO-IgG-seropositive patients. In contrast, NMO-IgG-seronegative children with NMO more commonly have a monophasic course (simultaneous occurrence of optic neuritis and transverse myelitis) and do not require remission-maintaining immunotherapy, but close surveillance is advised. Current clinical, pathological, and pathogenetic knowledge is reviewed with a focus on clinical presentation, neuroimaging findings, serological investigations, and treatment of children with disorders within the spectrum of central nervous system aquaporin-4 autoimmunity.