Distinguishing functional from primary tics: a study of expert video assessments.

BACKGROUND: Reliably applied criteria to differentiate functional from primary tics are lacking. In the absence of biological markers, the development of new diagnostic criteria to assist clinicians is predicated on expert judgement and consensus. This study examines the level of diagnostic agreement of experts in tic disorders using video footage and clinical descriptions. METHODS: Using a two-part survey, eight experts in the diagnosis and management of tics were first asked to study 24 case videos of adults with primary tics, functional tics or both and to select a corresponding diagnosis. In the second part of the survey, additional clinical information was provided, and the diagnosis was then reconsidered. Inter-rater agreement was measured using Fleiss' kappa. In both study parts, the factors which influenced diagnostic decision-making and overall diagnostic confidence were reviewed. RESULTS: Based on phenomenology alone, the diagnostic agreement among the expert raters was only fair for the pooled diagnoses (κ=0.21) as well as specifically for functional (κ=0.26) and primary tics (κ=0.24). Additional clinical information increased overall diagnostic agreement to moderate (κ=0.51) for both functional (κ=0.6) and primary tics (κ=0.57). The main factors informing diagnosis were tic semiology, age at tic onset, presence of premonitory urges, tic suppressibility, the temporal latency between tic onset and peak severity, precipitants and tic triggers and changes in the overall phenotypic presentation. CONCLUSIONS: This study confirmed that in the absence of clinical information, the diagnostic distinction between primary and functional tics is often difficult, even for expert clinicians.

S1P receptor modulators in Multiple Sclerosis: Detecting a potential skin cancer safety signal.

INTRODUCTION: S1P receptor modulators are oral Disease-Modifying Therapies (DMTs) for Multiple Sclerosis, which were associated with cases of basal cell carcinoma in clinical trials. This study aims at investigating in a real-world adverse event reporting system whether S1P receptor modulators increase the risk of skin cancer reporting, compared to other DMTs. METHODS: Adverse event reports from the FDA Adverse Event Reporting System (FAERS) were extracted, cleaned, and analyzed from 2004Q1 until 2020Q4. The crude and adjusted Reported Odds Ratios (cROR, aROR) for the outcomes: basal cell carcinoma, squamous cell carcinoma, or melanoma were calculated for all DMTs. In a sensitivity analysis, we looked at each outcome separately. RESULTS: The aROR (95%CI) of siponimod was: 9.68 (5.48-15.79) and of fingolimod 4.54 (3.86-5.32), indicating a safety signal of S1P receptor modulators for skin cancer. Ozanimod had only 52 complete reports without any cases. In the sensitivity analysis, siponimod showed a signal only for basal cell carcinoma: 22.83 (12.27-38.83), while fingolimod for all outcomes separately, including melanoma: 3.02 (2.31-3.89). Notably, among the other DMTs, alemtuzumab: 4.40 (2.98-6.25) and cladribine: 3.28 (1.17-7.13) presented also a signal for disproportionate reporting, while ocrelizumab showed a signal in the sensitivity analysis only for melanoma 2.55 (1.21-4.65). CONCLUSIONS: S1P receptors seem to increase skin cancer reporting on FAERS, and the association is strongest for basal cell carcinomas. Therefore, close dermatologic surveillance before- and during therapy is needed. Whether fingolimod and ocrelizumab also increase the risk of melanoma needs further investigation.