Abnormal functional connectivity in radiologically isolated syndrome: A resting-state fMRI study.

BACKGROUND: Radiologically isolated syndrome (RIS) patients might have psychiatric and cognitive deficits, which suggests an involvement of major resting-state functional networks. Notwithstanding, very little is known about the neural networks involved in RIS. OBJECTIVE: To examine functional connectivity differences between RIS and healthy controls using resting-state functional magnetic resonance imaging (fMRI). METHODS: Resting-state fMRI data in 25 RIS patients and 28 healthy controls were analyzed using an independent component analysis; in addition, seed-based correlation analysis was used to obtain more information about specific differences in the functional connectivity of resting-state networks. Participants also underwent neuropsychological testing. RESULTS: RIS patients did not differ from the healthy controls regarding age, sex, and years of education. However, in memory (verbal and visuospatial) and executive functions, RIS patients' cognitive performance was significantly worse than the healthy controls. In addition, fluid intelligence was also affected. Twelve out of 25 (48%) RIS patients failed at least one cognitive test, and six (24.0%) had cognitive impairment. Compared to healthy controls, RIS patients showed higher functional connectivity between the default mode network and the right middle and superior frontal gyri and between the central executive network and the right thalamus (pFDR < 0.05; corrected). In addition, the seed-based correlation analysis revealed that RIS patients presented higher functional connectivity between the posterior cingulate cortex, an important hub in neural networks, and the right precuneus. CONCLUSION: RIS patients had abnormal brain connectivity in major resting-state neural networks and worse performance in neurocognitive tests. This entity should be considered not an "incidental finding" but an exclusively non-motor (neurocognitive) variant of multiple sclerosis.

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.

Exposición a fármacos modificadores de la enfermedad durante el embarazo en esclerosis múltiple: estudio prospectivo / Pregnancy exposure to disease-modifying drugs in multiple sclerosis: a prospective study

INTRODUCCIÓN: En esclerosis múltiple (EM), la exposición fetal a fármacos modificadores de la enfermedad (FME) conlleva distintos grados de riesgo. OBJETIVO: analizar nuestra experiencia en relación con los casos de exposición fetal involuntaria a FME. PACIENTES Y MÉTODOS: Estudio observacional. Se analizaron los datos clínico-obstétricos de una cohorte de pacientes con EM, entre 2007 y 2017. Grupo EM: pacientes con EM con embarazos expuestos a FME. Grupo control: pacientes con EM no expuestas y embarazadas sanas. RESULTADOS: Hubo un total de 68 embarazos en pacientes con EM. Control: 56 mujeres sanas. Grupo EM expuestas a FME durante embarazo: 13; bajo peso al nacer: 2(15%); parto pretérmino: 0. Grupo EM no expuestas a FME: 55; 22 (40%) suspendieron FME previo embarazo; 33 (60%) naïve; bajo peso al nacer: 5 (9%); pretérmino: 7 (12%). Grupo mujeres sanas: bajo peso al nacer, 6 (11%); parto pretérmino, 6 (11%). No hubo diferencias clínicas estadísticamente significativas entre pacientes EM. Tampoco hubo diferencias en peso al nacer, tiempo de gestación o morbilidad obstétrica en expuestas a FME. CONCLUSIONES: No hubo diferencias clínicas estadísticamente significativas, ni mayor morbilidad obstétrica, entre pacientes expuestas a FME, no expuestas y embarazadas sanas

INTRODUCTION: In multiple sclerosis (MS), foetal exposure to disease-modifying drugs (DMDs) carries varying degrees of risk. We sought to analyse the clinical and obstetric outcomes of MS patients (MSp) exposed to DMDs during pregnancy. PATIENTS AND METHODS: Observational study. We analysed the clinical-obstetric data of a cohort MSp, who became pregnant between 2007-2017. They were prospectively followed up during pregnancy and postpartum. CONTROL GROUP: healthy pregnant women (HPW) and MSp unexposed to DMDs. RESULTS: Sixty-eight pregnancies in MSp. Fifty-six HPW. Thirteen MSp were exposed to DMDs during pregnancy. Obstetric outcome: 2 (15%) infants had low birth weight, no preterm deliveries. Fifty-five MSp were not exposed to DMDs: 22 (40%) discontinued DMD before pregnancy, 33(60%) naïve. Five infants (9%) had low birth weight and 7 (12%) were preterm. HPW: 56. Low birth weight 6 (11%), preterm delivery 6 (11%). There were no differences in relapse incidence during pregnancy-puerperium between MSp groups. There were no differences in birth weight, gestation time, delivery-caesarean section. We found no special obstetric morbidity in women exposed to DMDs. CONCLUSIONS: There were no significant differences in the clinical and obstetric variables analysed between pregnant women exposed to DMDs, unexposed, and HPW

Pregnancy exposure to disease-modifying drugs in multiple sclerosis: a prospective study. / Exposición a fármacos modificadores de la enfermedad durante el embarazo en esclerosis múltiple: estudio prospectivo.

INTRODUCTION: In multiple sclerosis (MS), foetal exposure to disease-modifying drugs (DMDs) carries varying degrees of risk. We sought to analyse the clinical and obstetric outcomes of MS patients (MSp) exposed to DMDs during pregnancy. PATIENTS AND METHODS: Observational study. We analysed the clinical-obstetric data of a cohort MSp, who became pregnant between 2007-2017. They were prospectively followed up during pregnancy and postpartum. CONTROL GROUP: healthy pregnant women (HPW) and MSp unexposed to DMDs. RESULTS: Sixty-eight pregnancies in MSp. Fifty-six HPW. Thirteen MSp were exposed to DMDs during pregnancy. Obstetric outcome: 2 (15%) infants had low birth weight, no preterm deliveries. Fifty-five MSp were not exposed to DMDs: 22 (40%) discontinued DMD before pregnancy, 33(60%) naïve. Five infants (9%) had low birth weight and 7 (12%) were preterm. HPW: 56. Low birth weight 6 (11%), preterm delivery 6 (11%). There were no differences in relapse incidence during pregnancy-puerperium between MSp groups. There were no differences in birth weight, gestation time, delivery-caesarean section. We found no special obstetric morbidity in women exposed to DMDs. CONCLUSIONS: There were no significant differences in the clinical and obstetric variables analysed between pregnant women exposed to DMDs, unexposed, and HPW.

Cerebral amyloid angiopathy-related transient focal neurological episodes: A transient ischemic attack mimic with an increased risk of intracranial hemorrhage.

BACKGROUND: Transient focal neurological episodes (TFNEs) are a recently recognized clinical presentation of cerebral amyloid angiopathy (CAA). Our aim was to describe the clinical and radiological features of a series of patients with AS. METHODS: We included 11 patients presenting with recurrent transient focal neurological symptoms and radiological features related to CAA. RESULTS: Mean age was 76,6 and 5 patients were women. All patients reported transient, stereotyped, and recurrent episodes (6 patients had >10 episodes). Gradual spread of the symptoms was recorded in 9 patients. Initially, 3 patients were misdiagnosed as having recurrent transient ischemic attack (TIA), 6 as having seizures, and 2 as having both. Two patients were prescribed antiplatelet therapy. A cerebral MRI with T2* gradient-recalled echo sequence revealed cortical superficial siderosis (cSS) in 5 patients, cortical microbleeds in 1 patient, and both features in 5 cases. After a median follow-up of 36 months, intracranial hemorrhage (ICH) was recorded in 4 patients. All 4 had cSS in the previous cerebral MRI, and 1 was on antiplatelet therapy. CONCLUSION: CAA-related TFNEs are an underdiagnosed entity, often mimicking TIA, seizures, or migraine aura. This misdiagnosis can lead to the prescription of antiplatelet or anticoagulant therapy, which increases the risk of ICH. Our results suggest that cSS might be a radiological marker that is closely related to an increased risk of bleeding. A T2* gradient-recalled echo MRI should be performed in elderly patients with transient focal neurological symptoms suggestive of CAA.

Deterioro cognitivo en el paciente muy anciano: estudio retrospectivo en una consulta de neurología / Cognitive impairment in very elderly patients: a retrospective study in a neurology service

Introducción. Una considerable proporción de pacientes muy ancianos con deterioro cognitivo son atendidos en las consultas generales de neurología, pero existen pocos estudios acerca de las características clínicas de estos pacientes. Objetivo. Describir los antecedentes y rasgos clínicos de los pacientes muy ancianos que acuden a consulta general de neurología por quejas o sospecha de deterioro cognitivo. Pacientes y métodos. Se estudio retrospectivamente a 336 pacientes (296 pacientes < 85 años frente a 40 pacientes ≥ 85 años) que habían sido remitidos en su mayoría desde la atención primaria. El rendimiento cognitivo se midió mediante el test minimental de Folstein, y la situación clínica global (cognitiva y funcional), mediante la escala de estatificación clínica de la demencia. Resultados. Los pacientes de más edad presentaban con mayor frecuencia deterioro cognitivo (alteración cognitiva leve o demencia), tanto en la primera visita como en la visita de seguimiento al cabo de un ano (p < 0,0005). No se encontraron diferencias en el tiempo desde el inicio de los síntomas (2,0 +/- 2,1 frente a 1,5 +/- 1,4 años), el tipo de síntomas ni la comorbilidad. La enfermedad de Alzheimer fue el diagnostico etiológico final más frecuente en los dos grupos de edad (82,4% frente a 75%; p > 0,05). Conclusiones. Los pacientes muy ancianos estudiados en la consulta de neurología presentan con mayor frecuencia deterioro cognitivo, a pesar de tener un tiempo de evolución y una sintomatología similares. Estos resultados podrían explicarse desde la hipótesis de la reserva cerebral y de la patología cerebral combinada

Introduction. A considerable proportion of very elderly patients with cognitive impairment are attended in the general neurology offices. There are few studies about the clinical characteristics of these patients. Aim. To describe the background and clinical features of very elderly patients who come to the general neurology clinic due to cognitive complaints or suspected cognitive impairment. Patients and methods. We retrospectively studied 336 patients (296 patients < 85 years vs. 40 patients ≥ 85 years of age) who had been mostly referred by primary care physicians. Cognitive performance was measured by the Mini-Mental State Examination and the overall (i.e., cognitive and functional) clinical situation was measured by the Clinical Dementia Rating scale. Results. Older patients had more frequently cognitive impairment (mild cognitive impairment or dementia), both at the first visit and at the one-year follow-up visit (p < 0.0005). No differences were found in symptom duration (2.0 +/- 2.1 vs. 1.5 +/- 1.4 years), type of symptoms, or comorbidity. Alzheimer's disease was the most frequent etiological diagnosis in both age groups (82.4% vs. 75.0%; p > 0.05). Conclusions. Very elderly patients studied in the neurology office have a higher risk of presenting cognitive impairment, despite being comparable in terms of symptoms and time of evolution. These results could be explained from the hypotheses of brain reserve and combined brain pathology