Early predictive risk factors for dimethyl fumarate-associated lymphopenia in patients with multiple sclerosis.

BACKGROUND: Lymphopenia is a major concern in MS patients treated with dimethyl-fumarate (DMF) as it increases the risk of progressive multifocal leukoencephalopathy. A pronounced reduction in absolute lymphocyte counts (ALCs) early after treatment initiation has been suggested to be associated with the occurrence of lymphopenia thereafter. OBJECTIVES: To identify risk factors for DMF-induced lymphopenia and evaluate whether the degree of decrease in the ALCs three months after initiation of DMF treatment is a predictor of the subsequent development of lymphopenia. METHODS: In this real-world Spanish prospective multicenter study conducted in MS patients who started DMF between 2014 and 2019, we analyzed the association between DMF-related lymphopenia and the percentage of early ALCs decline using regression models, considering both, significant lymphopenia (grades 2 + 3) and severe lymphopenia (grade 3). The cutoff values of early ALCs declines were obtained using the ROC curve. RESULTS: Among 532 MS patients treated with DMF, 193 (36.3%) developed any grade of lymphopenia. Older age and lower ALCs at treatment onset predicted the risk for lymphopenia but the best predictive risk factor was the reduction of ALCs within the three first months of treatment. Specifically, a reduction in ALCs≥21.2% was associated with a 6.5-fold higher risk of developing significant lymphopenia, and a decrease in ALCs≥40.2% with a 12.7-fold higher risk of developing severe lymphopenia. CONCLUSIONS: A pronounced reduction in ALCs early after initiation of DMF in MS patients is the best predictive risk factor for the subsequent development of significant lymphopenia.

Anti-JC virus seroprevalence in a Spanish multiple sclerosis cohort: JC virus seroprevalence in Spain.

OBJECTIVE: To estimate the seroprevalence of anti-JCV antibodies, seroconverting rates and evolution of antibody levels in a multiple sclerosis (MS) Spanish cohort. METHODS: Multicenter, retrospective cross-sectional and longitudinal study. The JCV seroprevalence was analyzed in 711 MS patients by using 1st (STRATIFY-1) and 2nd generation (STRATIFY-2) two-step ELISA over 2.65 (±0.97) years. Seroconversion rate was obtained over 2 samples from 314 patients, and index stability from 301 patients with 3 or more samples available. The effect of each ELISA generation, demographics, clinical characteristics and therapy on seroprevalence was assessed by logistic regression. RESULTS: The overall anti-JCV seroprevalence was 55.3% (51.6-58.9), similar across regions (p=0.073). It increased with age (p<0.000) and when STRATIFY-2 was used (60.5%, p=0.001). Neither sex nor immunosuppressive therapy had any influence. Yearly seroconversion rate was 7% (considering only STRATIFY-2). Serological changes were observed in 24/301 patients, 5.7% initially seropositive reverted to seronegative and 7% initially seronegative changed to seropositive and again to seronegative, all these cases had initial index values around the assay's cut-off. CONCLUSIONS: JCV seroprevalence in Spanish MS patients was similar to that reported in other European populations. Changes in serostatus are not infrequent and should be considered in clinical decisions.

Butyrylcholinesterase, ApoE and Alzheimer's disease in a population from the Canary Islands (Spain).

AIM: Cholinergic dysfunction is a major neurochemical feature in Alzheimer's disease (AD), accountable for many cognitive dysfunctions and some psychiatric symptoms. Butyrylcholinesterase (BChE) is one of the cholinesterases with increased activity in the brain of Alzheimer's patients. Several mutations code for different BChE, such as the K variant, which is the most common and is capable of reducing BChE activity by 30%. We studied the relationship between this K variant and Alzheimer's disease in our population from the Canary Islands (Spain). PATIENTS AND METHODS: We used DNA PCR-RFLP techniques to compare 282 patients who had been diagnosed with probable Alzheimer's disease--according to NINCS-ADRDA criteria--with 312 control subjects confirmed to be free of cognitive impairment as assessed by using the CAMDEX cognitive subscale CAMCOG. RESULTS: In our population the K variant of BChE is linked to the age of diagnosis of Alzheimer's disease, since AD individuals with this allele presented the disease at a later stage. No other susceptibility relations are exposed in this study. In addition, the BChE allelic frequencies in our population are higher than those previously reported.

Evaluation of maximal respiratory pressures in myasthenia gravis. Prognostic value.

We assess the prognosis of mild forms of myasthenia gravis (MG) by maximal respiratory pressures (MRP) and single fiber electromyography (SFEMG). Fifty MG patients (12 form I, 21 form IIa and 17 form IIb) are valued by MRP [maximal expiratory pressure (MEP) and maximal inspiratory pressure (MIP)] and SFEMG, and are followed-up clinically. We have found in form I patients developing form IIa and form IIa worsening to form IIb, MEP and MIP mean relative values significantly lower than the rest. Inversely, IIb form patients improving to IIa form display MIP mean relative values higher than the rest; no difference appears with MEP. A reduction under 50% of fifth-percentile implies clinical deterioration in forms I and IIa, while its surpassing in IIb form suggests a tendency to improvement. No evident differences are found by SFEMG. MRP allow the follow-up of MG patients and could warn us of a clinical prognosis.