RESUMO
BACKGROUND: Calcitriol, the active form of vitamin D (also known as 1,25-dihydroxycholecalciferol), improves the phenotype and increases frataxin levels in cell models of Friedreich ataxia (FRDA). OBJECTIVES: Based on these results, we aimed measuring the effects of a calcitriol dose of 0.25 mcg/24h in the neurological function and frataxin levels when administered to FRDA patients for a year. METHODS: 20 FRDA patients where recluted and 15 patients completed the treatment for a year. Evaluations of neurological function changes (SARA scale, 9-HPT, 8-MWT, PATA test) and quality of life (Barthel Scale and Short Form (36) Health Survey [SF-36] quality of life questionnaire) were performed. Frataxin amounts were measured in isolated platelets obtained from these FRDA patients, from heterozygous FRDA carriers (relatives of the FA patients) and from non-heterozygous sex and age matched controls. RESULTS: Although the patients did not experience any observable neurological improvement, there was a statistically significant increase in frataxin levels from initial values, 5.5 to 7.0 pg/µg after 12 months. Differences in frataxin levels referred to total protein levels were observed among sex- and age-matched controls (18.1 pg/µg), relative controls (10.1 pg/µg), and FRDA patients (5.7 pg/µg). The treatment was well tolerated by most patients, and only some of them experienced minor adverse effects at the beginning of the trial. CONCLUSIONS: Calcitriol dosage used (0.25 mcg/24 h) is safe for FRDA patients, and it increases frataxin levels. We cannot rule out that higher doses administered longer could yield neurological benefits. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
RESUMO
BACKGROUND: Intrathecal immunoglobulin synthesis (ITS) plays a crucial role in the diagnosis of multiple sclerosis (MS). Traditionally, the gold standard method for detecting ITS has been through the analysis of oligoclonal bands (OCB). However, the paradigm has shifted with the introduction of the free kappa light chains (FKLC) method. In fact, a recent consensus recommends evaluating FKLC index (FKLCi) as the primary approach and reserving oligoclonal bands with borderline results. The objective of our study is to investigate the diagnostic efficiency of combining FKLC with other methods to predict ITS while minimizing the reliance on OCB. METHODS: A total of 192 patients were included in the study, consisting of 145 individuals diagnosed with multiple sclerosis (pwMS) and 46 with other neurological diseases (controls). Among the MS cases, 100 patients were assigned to the Training Cohort (TC), while an external Validation Cohort (VC) comprised of 45 MS patients was established. Diagnostic efficiency was assessed for FKLCi, OCB, Link index, and the Reiber formula for IgG and FKLC. Optimal cutoff values for Link index and FKLCi were also determined. The last procedure was developed for diverse algorithms using the parameters mentioned above, which included the optimal cutoffs previously obtained. The calculations were conducted independently for both the TC and the VC, as well as for a composite cohort formed by combining data from all patients (OC) RESULTS: One algorithm, named KRO, was developed based on the determination of FKLCi and Reiber Formula as the primary diagnostic parameters. For cases where the FKLCi result was mildly increased, OCB was utilized as a supplementary test. The KRO algorithm demonstrated superior diagnostic accuracy in the OC (89%), resulting in a reduction of OCB consumption by 91%. DISCUSSION: The KRO algorithm demonstrated superior sensitivity and accuracy although lower specificity and NPV compared to the use of FKLCi and OCB alone. The present research aligns with the new consensus recommendations regarding the diagnostic approach. Our findings indicate that employing a combined marker approach via KRO could prove to be a proficient screening tool for multiple sclerosis. This approach also holds the potential to address inherent limitations associated with each individual marker. However, to further validate and solidify the efficacy of our algorithm, additional studies involving larger cohorts are warranted.
