Clinical, laboratory features, and prognostic factors in adult acute transverse myelitis: an Italian multicenter study.

OBJECTIVES: We compared the clinical, laboratory, and radiological features of different subgroups of acute transverse myelitis (ATM) diagnosed according to the criteria established by the Transverse Myelitis Consortium Working Group (TMCWG) as well as of non-inflammatory acute transverse myelopathies (NIATM) to identify possible short- and long-term prognostic factors. METHODS: A multicenter and retrospective study comprising 110 patients with ATM and 15 NIATM admitted to five Italian neurological units between January 2010 and December 2014 was carried out. RESULTS: A significantly higher frequency of isolated sensory disturbances at onset in ATM than in NIATM patients (chi-square = 14. 7; P = 0.005) and a significantly higher frequency of motor symptoms in NIATM than ATM (chi-square = 12.4; P = 0.014) was found. ATM patients with high disability at discharge had more motor-sensory symptoms without (OR = 3.87; P = 0.04) and with sphincter dysfunction at onset (OR = 7.4; P = 0.0009) compared to those with low disability. Higher age (OR = 1.08; P = 0.001) and motor-sensory-sphincter involvement at onset (OR = 9.52; P = 0.002) were significantly associated with a high disability score at discharge and after a median 1-year follow-up. CONCLUSIONS: The diagnosis of ATM may prevail respect to that of NIATM when a sensory symptomatology at onset occurs. In ATM, patients older and with motor-sensory involvement with or without sphincter impairment at admission could experience a major risk of poor prognosis both at discharge and at longer time requiring a timely and more appropriate treatment.

Association of circulating anti-CD64 IgM levels with favourable long-term clinical outcomes in multiple sclerosis patients.

Circulating levels of IgM anti-CD64, an immunosuppressive antibody recently identified in long-term stable multiple sclerosis (MS) patients, were found to fluctuate over time in MS patients. Antibody-positive patients showed a significantly lower annualized relapse rate value as well as reached sustained disability worsening and had a relapse in a significantly longer median time than those without antibody. Disease-modifying therapies (DMTs) only were the covariate influencing both the relapse occurrence and the disability accrual. Serum IgM anti-CD64 levels are associated with maintenance of clinical stability in MS and may be tested as a candidate biomarker predictive of benign course and favourable long-term response to DMTs treatment.

Longitudinal quantitative assessment of macula during therapy with fingolimod in relapsing-remitting multiple sclerosis.

PURPOSE: Fingolimod is the first oral drug approved for treatment of relapsing-remitting multiple sclerosis (RR-MS), and it has potential macular side effects. Despite the qualitative evidence of macular oedema under treatment, longitudinal quantitative assessment is lacking. To address this issue, we measured macular volume and central foveal thickness in a cohort of MS patients on fingolimod over 12 months of treatment. METHODS: Central foveal thickness (CFT) and total macular volume (TMV) were longitudinally recorded with spectral-domain optical coherence tomography in a cohort of 23 RR-MS patients treated with fingolimod at baseline, 3, 6 and 12 months. OCT parameters were analysed considering previous history of optic neuritis (ON). Comparison of means was performed with variance analysis (ANOVA). RESULTS: Macular oedema occurred in none of the patients. Comparing both groups of patients (with and without previous ON), no statistically significant difference was found during the follow-up both for CFT and TMV (p = 0.99 and p = 0.96, respectively) although a slight early but not significant TMV reduction was detected. CONCLUSIONS: In our cohort, therapy with fingolimod did not cause any change in CFT and TMV in MS patients during a 12-month follow-up independent of previous ON.

Fingolimod reduces circulating tight-junction protein levels and in vitro peripheral blood mononuclear cells migration in multiple sclerosis patients.

There are no data on the effects of fingolimod, an immunomodulatory drug used in treatment of multiple sclerosis (MS), on circulating tight-junction (TJ) protein levels as well as on peripheral blood mononuclear cells (PBMC) migration. Serum TJ protein [occludin (OCLN), claudin-5 (CLN-5) and zonula occludens-1 (ZO-1)] levels, sphingosine-1 phosphate 1 (S1P1) receptor expression on circulating leukocyte populations as well as in vitro PBMC migration were longitudinally assessed in 20 MS patients under 12-months fingolimod treatment and correlated with clinical and magnetic resonance imaging (MRI) parameters. After 12 months of treatment, a significant reduction of mean relapse rate as well as number of active lesions at MRI was found. TJ protein levels significantly decreased and were associated with reduction of S1P1 expression as well as of PBMC in vitro migratory activity. A significant correlation of CLN-5/OCLN ratio with new T2 MRI lesions and a significant inverse correlation of CLN-5/ZO-1 ratio with disability scores were found. These findings support possible in vivo effects of fingolimod on the blood-brain barrier (BBB) functional activity as well as on peripheral cell trafficking that could result in avoiding passage of circulating autoreactive cells into brain parenchyma. Circulating TJ protein levels and respective ratios could be further studied as a novel candidate biomarker of BBB functional status to be monitored in course of fingolimod as well as of other immunomodulatory treatments in MS.