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INTRODUCTION: Ocrelizumab, an antiCD-20 antibody, is the only drug approved to treat patients with primary progressive multiple sclerosis (pwPPMS). Not all candidates receive this treatment due to prescription limitations. Rituximab, another antiCD-20 antibody, has been used off-label in pwPPMS before and after ocrelizumab approval. However, studies comparing effectiveness of both drugs are lacking. OBJECTIVE: To evaluate effectiveness of rituximab and ocrelizumab in pwPPMS under real-life conditions. METHODS: We conducted a multicentric observational study of pwPPMS that started ocrelizumab or rituximab according to clinical practice, with a minimum follow-up of 1 year. Data was collected prospectively and retrospectively. Primary outcome was time to confirmed disability progression at 3 months (CDW). Secondary outcome was serum neurofilament light chain levels (sNFL) at the end of follow-up. RESULTS: 95 out 111 pwPPMS fulfilled inclusion criteria and follow-up data availability: 49 (51.6%) received rituximab and 46 (48.4%) ocrelizumab. Rituximab-treated patients had significantly higher baseline EDSS, disease duration and history of previous disease-modifying treatment (DMT) than ocrelizumab-treated patients. After a mean follow-up of 18.3 months (SD 5.9), 26 patients experienced CDW (21.4%); 15 (30.6%) in the rituximab group; and 11 (23.9%) in the ocrelizumab group. Survival analysis revealed no differences in time to CDW. sNFL were measured in 60 patients and no differences between groups were found. INTERPRETATION: We provide real-world evidence of effectiveness of ocrelizumab and rituximab in pwPPMS. No differences in time to CDW were found between treatments. However, this study cannot establish equivalence of treatments and warrant clinical trial to confirm our findings.

Mutations in the MAPT gene cause frontotemporal dementia with tau deposits. We report the novel p.P397S MAPT variant in eight subjects from five apparently nonrelated families suffering from frontotemporal dementia with autosomal dominant pattern of inheritance. In silico analysis reported conflicting evidence of pathogenicity. The segregation analysis support that this variant is likely pathogenic. The mean age at onset (61.4 years) and mean disease duration (13.9 years) of these subjects and their affected relatives were significantly higher compared with our series of p.P301L MAPT mutation carriers. These findings suggest that p.P397S variant could be a new MAPT mutation associated with a less aggressive phenotype than other MAPT mutations.

Background For safety reasons multiple sclerosis (MS) treatment guidelines recommend stopping or delaying the onset of disease-modifying therapies (DMT) before a planned pregnancy, but disease stability after DMT discontinuation is not well studied. The objective of this study is to describe the course of MS in patients who interrupted DMT before a planned pregnancy. Methods This was a retrospective study using 2008–2016 data from a multicenter register of pregnancies in women with MS. In this paper, we present data from the subgroup of women with relapsing-remitting MS (RRMS) who interrupted DMT to try to conceive. Data from 1 and 3 years before DMT interruption, the period between DMT interruption and conception or resuming DMT, during pregnancy and one year postpartum were analyzed. Annualized relapse rates (ARR), Expanded Disability Status Scale (EDSS) scores, and magnetic resonance imaging (MRI), obstetric, and neonatal data were collected. Results Twenty-seven women interrupted DMT (19 β-interferon, 5 glatiramer acetate, 2 natalizumab and 1 fingolimod) to try to conceive. After a mean of 10.6 months 6 women stopped trying to conceive and resumed DMT, while 21 women became pregnant after a mean of 7.0 months. In the overall cohort, in the period from when DMT was discontinued to when pregnancy was confirmed or DMT resumed, the ARR was 1.08, which was significantly higher than the ARR 1 year (0.44; p = 0.01) and 3 years (0.4; p = 0.06) before DMT discontinuation. The mean EDSS score when pregnancy was confirmed or DMT resumed was significantly higher than at DMT discontinuation (1.8 vs 1.36, p = 0.011). In the subgroup of patients who became pregnant, the ARR in the untreated period before pregnancy was 0.98, which was significantly higher than the ARR 1 year (0.38; p = 0.03) and 3 years (0.39; p = 0.0077) before DMT discontinuation. The ARR decreased to 0.51 during pregnancy and then increased to 0.76 during the first postpartum trimester (not significant). One year after delivery, the mean EDSS score (1.86) was significantly higher than at DMT cessation (1.35, p = 0.027) or pregnancy confirmation (1.45, p = 0.026). Patients who suffered relapses following DMT cessation before becoming pregnant had an 11-fold higher risk of relapse during pregnancy (relative risk [RR] = 11.1 [95%CI 1.6, 75], p = 0.002) and a 3-fold higher risk during the postpartum year (RR = 3.0 [95%CI 1.3,6.6], p = 0.007) than those who did not suffer relapses in period between DMT withdrawal and pregnancy. Conclusions In this retrospective registry study, discontinuation of DMT (mostly immunomodulatory drugs), to try to conceive resulted in an increase in MS relapse rates and disability progression.

Aim: To examine evolution in activities of daily living (ADL) in patients with multiple sclerosis spasticity during long-term use of tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray. Methods: Functional impairment was assessed retrospectively (prior to start of treatment) and at the present moment using a 16-item ADL survey; results were compared. A control group without add-on THC:CBD oromucosal spray was included to investigate possible recall bias. Results: ADL was maintained or slightly improved with THC:CBD oromucosal spray across treatment time (mean 31.9 months) including significant improvement in ‘standing up’ (p

To study the efficacy of interferon beta (IFN beta) and glatiramer acetate (GA) related to the presence of oligoclonal M bands (OCMB) in the cerebrospinal fluid in relapsing-remitting multiple sclerosis (RRMS). This is an observational, multicenter and retrospective study with prospectively collected data of patients that started treatment with IFN beta or GA. Treatment decision was made blinded to the OCMB status. Time to first attack after starting therapy was compared by using Kaplan-Meier curves, and adjustment by Cox regression analysis was performed. Two hundred and fifty-six patients entered in the study (141-55% received IFN beta; 115-45% received GA). After a mean follow-up of 41 and 65 months, 54.7% of patients remained free from further attacks (RF). The proportion of RF patients was higher in the GA group than in the IFN beta group (72.2 vs. 40.4%, p < 0.001). The IFN beta patients with OCMB+ presented the poorest response, 31.3% RF vs. 48.1% in IFN beta without OCMB, p = 0.03. OCMB in CSF could be a biomarker of treatment response in multiple sclerosis.

The main objective of our work is to describe the long-term results of myeloablative autologous hematopoietic stem cell transplant (AHSCT) in multiple sclerosis patients. Patients that failed to conventional therapies for multiple sclerosis (MS) underwent an approved protocol for AHSCT, which consisted of peripheral blood stem cell mobilization with cyclophosphamide and granulocyte colony-stimulating factor (G-CSF), followed by a conditioning regimen of BCNU, Etoposide, Ara-C, Melphalan IV, plus Rabbit Thymoglobulin. Thirty-eight MS patients have been transplanted since 1999. Thirty-one patients have been followed for more than 2 years (mean 8.4 years). There were 22 relapsing-remitting multiple sclerosis (RRMS) patients and 9 secondary progressive multiple sclerosis (SPMS) patients. No death related to AHSCT. A total of 10 patients (32.3%) had at least one relapse during post-AHSCT evolution, 6 patients in the RRMS group (27.2%) and 4 in the SPMS group (44.4%). After AHSCT, 7 patients (22.6%) experienced progression of disability, all within SP form. By contrast, no patients with RRMS experienced worsening of disability after a median follow-up of 5.4 years, 60% of them showed a sustained reduction in disability (SRD), defined as the improvement of 1.0 point in the expanded disability status scale (EDSS) sustains for 6 months (0.5 in cases of EDSS >= 5.5). The only clinical variable that predicted a poor response to AHSCT was a high EDSS in the year before transplant. AHSCT using the BEAM-ATG scheme is safe and efficacious to control the aggressive forms of RRMS.

Aim: To assess potential predictors for burden and depression among caregivers of relapsing-remitting multiple sclerosis patients in Spain. Family functioning and social support were also assessed. Patients & methods: Multicenter and cross-sectional study in relapsing-remitting multiple sclerosis adult patients and their respective informal caregivers (n = 180). Assessment performed: Zarit Scale (Burden), Center for Epidemiologic Studies Depression-7 Scale (depression), Family APGAR (Adaptation, Partnership, Growth, Affection, Resolve) Questionnaire (family functioning) and Duke UNC-11 Functional Social Support Questionnaire (social support). Multivariate logistic regression analysis assessed burden and depression predictors among caregivers. Results: Caregivers suffered burden (19.4%) and depression (20.6%) and perceived poor social support (9.4%) and family dysfunction (10.6%). Burden predictors were patient's degree of disability, caregiver time and number of medications administered to patient. Depression predictors were patient's age and daily caregiving time. Conclusion: The factors reported here could help clinicians to identify caregiver groups particularly at risk of burden and depression for timely intervention.

Lung cancer represents one of the most common malignant diseases. Many investigations are used in the staging study including, most recently, PET. We present a case of cystic cerebral metastases (with no oedema) from a small cell carcinoma which were not detected by PET.

Introduccion. Los estudios postautorizacion son importantes para confirmar si los resultados de los ensayos clinicos se reproducen en la practica clinica habitual. Objetivo. Evaluar la efectividad y seguridad del fingolimod en la practica clinica en la provincia de Alicante. Pacientes y metodos. Estudio multicentrico retrospectivo de pacientes con esclerosis multiple remitente tratados con fingolimod. Se recogen las caracteristicas demograficas, clinicas y farmacologicas. Se describe la efectividad del farmaco –tasa anualizada de brotes (TAB) y porcentaje de pacientes libres de brotes– al ano y a los dos anos de tratamiento en relacion con el ano previo y datos de efectos secundarios. Resultados. Se incluyo a 89 pacientes. El tratamiento previo fue inmunomodulador (interferon beta o acetato de glatiramero) en 54 pacientes y natalizumab en 32. Cincuenta pacientes cambiaron por fracaso con el inmunomodulador y 31 por serologia positiva del virus JC (VJC+). La TAB global disminuyo el 67,3% el primer ano (p < 0,0001) y el 84,1% el segundo (p = 0,0078). Disminuyo en los pacientes con fracaso del inmunomodulador (el 85,6% el primer ano, p < 0,0001; el 88,9% el segundo ano, p = 0,0039) y aumento de forma no significativa en los pacientes VJC+ en el primer ano. El porcentaje de pacientes libres de brotes en la poblacion global aumento del 32,6 al 68,1% en el primer ano (p < 0,0019) y al 82,6% en el segundo (p = 0,0215). Este aumento no se observo en los pacientes VJC+. Trece pacientes tuvieron efectos secundarios, que obligaron a la retirada del farmaco en dos de ellos. Conclusion. En la practica clinica de la provincia de Alicante, el fingolimod mostro una efectividad y una seguridad ligeramente superiores a las de los ensayos clinicos.

The objective in this paper is to compare the cumulative incidence and incidence density of therapy-related acute myeloid leukaemia in two cohorts of patients with multiple sclerosis treated with mitoxantrone, and with previously reported data in the literature. Six new cases of acute myeloid leukaemia were observed by prospectively following two Spanish series of 142 and 88 patients with worsening relapsing multiple sclerosis and secondary-progressive disease treated with mitoxantrone. A literature review shows 32 further cases of acute myeloid leukaemia reported, 65.6% of which are therapy-related acute promyelocytic leukaemia. Five cases in the cohorts fulfilled the diagnostic criteria for acute promyelocytic leukaemia, and one patient was diagnosed with pre-B-acute lymphoblastic leukaemia. Acute myeloid leukaemia latency after mitoxantrone discontinuation was 1 to 45 months. The accumulated incidence and incidence density was 2.82% and 0.62%, respectively, in the Valencian cohort, and 2.27% and 0.44% in the Catalonian cohort. In the only seven previously reported series, the accumulated incidence varied from 0.15% to 0.80%. The real incidence of acute myeloid leukaemia after mitoxantrone therapy in the multiple sclerosis population could be higher as evidenced by the growing number of cases reported. Haematological monitoring should continue for at least 5 years after the last dose of mitoxantrone. These data stress the necessity of re-evaluating this risk.

Different authors have described a variety of peripheral neuropathies during human immunodeficiency virus (HIV) infection. 1,2 Among them, we have found only one case of subacute ataxic neuropathy, described by Elder et al. 3 We now describe a case compatible with ganglioneuronitis both clinically and neurophysiologically, coincidental with HIV seroconversion. Report of a Case. In February 1992, a 28-year-old male intravenous drug abuser, with no other antecedents of interest, had an acute hepatitis 10 days before admission. Five days later, he developed a neurologic deficit with paresthesias and loss of tactile and pain sensation in his hands and feet, incoordination and slight weakness in all extremities, as well as inability to stand. On admission, he was afebrile and icteric and his liver edge was tender and palpable 5 cm below the right costal margin. Neurological examination revealed a severe distal loss of positional and vibratory senses, mild hypoalgesia and homogeneous