Reliability and construct validity of three self-report questionnaires assessing dual-task difficulties in people with multiple sclerosis: an international study.

OBJECTIVE: To evaluate the reliability and validity of the Dual-Tasking Questionnaire (DTQ), Dual-Task Screening-List (DTSL), and Dual-Task-Impact on Daily-life Activities Questionnaire (DIDA-Q). DESIGN: Multi-center, cross-sectional study SETTING: PwMS were recruited from seven MS centers across six countries (Belgium, Chile, Italy, Israel, Spain, and Turkey). PARTICIPANTS: A total of 356 pwMS (mean age 47.5±11.5, EDSS 3.79±1.83) were enrolled. INTERVENTIONS: Not applicable MAIN OUTCOME MEASURES: The reliability (internal consistency, test-retest, and measurement error) and construct validity (structural and convergent) were assessed. RESULTS: The DTQ, DTSL, and DIDA-Q demonstrated excellent test-retest reliability [Intraclass correlation coefficients (95% CI): 0.84 (0.80-0.87) to 0.90 (0.87-0.92)] and internal consistency (Cronbach's α: 0.86 to 0.96). As hypothesized, the three questionnaires showed a strong correlation with each other, moderate-to-strong correlations with other self-report questionnaires (perceived walking difficulties, fatigue, and fear of falling), and low-to-moderate correlations with cognitive information processing speed, manual dexterity, and dual-task walking performance (walking with word list generation task), showing convergent validity. The DIDA-Q exhibited systematically superior properties. These results were also verified in subsets from six different countries. In the structural validity analysis, all questionnaires displayed two main factors, allocated as 'motor-driven' and 'cognitive-driven' subscales. CONCLUSIONS: The DTQ, DTSL, and DIDA-Q have good-to-excellent measurement properties, with the highest properties observed in DIDA-Q. The use of these self-reported questionnaires can be used in research and clinical practice to assess the impact of dual-task difficulties on the daily life of ambulatory pwMS.

Age-dependent changes on TGFß1 Smad3 pathway modify the pattern of microglial cell activation.

Aging is the main risk factor for Alzheimer's disease. Among other characteristics, it shows changes in inflammatory signaling that could affect the regulation of glial cell activation. We have shown that astrocytes prevent microglial cell cytotoxicity by mechanisms mediated by TGFß1. However, whereas TGFß1 is increased, glial cell activation persists in aging. To understand this apparent contradiction, we studied TGFß1-Smad3 signaling during aging and their effect on microglial cell function. TGFß1 induction and activation of Smad3 signaling in the hippocampus by inflammatory stimulation was greatly reduced in adult mice. We evaluated the effect of TGFß1-Smad3 pathway on the regulation of nitric oxide (NO) and reactive oxygen species (ROS) secretion, and phagocytosis of microglia from mice at different ages with and without in vivo treatment with lipopolysaccharide (LPS) to induce an inflammatory status. NO secretion was only induced on microglia from young mice exposed to LPS, and was potentiated by inflammatory preconditioning, whereas in adult mice the induction of ROS was predominant. TGFß1 modulated induction of NO and ROS production in young and adult microglia, respectively. Modulation was partially dependent on Smad3 pathway and was impaired by inflammatory preconditioning. Phagocytosis was induced by inflammation and TGFß1 only in microglia cultures from young mice. Induction by TGFß1 was also prevented by Smad3 inhibition. Our findings suggest that activation of the TGFß1-Smad3 pathway is impaired in aging. Age-related impairment of TGFß1-Smad3 can reduce protective activation while facilitating cytotoxic activation of microglia, potentiating microglia-mediated neurodegeneration.

Frequency of diminished ovarian reserve in women with multiple sclerosis in Chile: An exploratory study.

INTRODUCTION: Multiple Sclerosis (MS) is a chronic disease affecting around 2.8 million people worldwide. Two-thirds are women, and the mean age at diagnosis is about 30 years old. Social trends are moving towards older age at first pregnancy, both in women with and without MS. OBJECTIVES: To determine the frequency of diminished ovarian reserve (DOR) through anti-Mullerian Hormone (AMH) measurement in women with MS at fertile age and Healthy Females (HF) in Chile. METHODS: Case-control, multicentric, cross-sectional study including relapsing-remitting people with MS (pwMS) between 18 and 40 years and sex and age-matched HF. We obtained a blood sample to determine AMH levels. We defined DOR as AMH <1.5 ng/mL and very-low AMH levels as <0.5 ng/mL. Also, we performed questions regarding reproductive decision-making. RESULTS: We included 79 sex and age-matched HF and 92 pwMS, median age 32(19-40) years, median disease duration 6 (1-17)years, median EDSS 1.0 (0-6), 95% were receiving disease-modifying therapy (DMT), 70% high-efficacy DMT and 37% with a treatment that contraindicates pregnancy. DOR was observed in 24% (n = 22) of the pwMS, compared to 14% (n = 11) of the HF (p = 0.09), while very-low AMH levels were observed in 7.6% (n = 7) of pwMS and none of the HF (p = 0.0166). We observed an inverse correlation between age and AMH levels. Age was the only significant risk factor for low AMH levels in pwMS (OR 1.14 95%CI(1.00-1-31), p = 0.04), including smoking, body mass index (BMI), hormonal contraception, autoimmune comorbidity, high/low-moderate efficacy DMT, and active disease as covariables. We did not find statistically significant differences in age at diagnosis, BMI, disease duration, EDSS, autoimmune comorbidity, use of hormonal contraception, or percentage of active disease between MS women with normal vs DOR. Over 70% of pwMS desired to become pregnant in the future, while 60% considered that the diagnosis of MS was a limitation for pregnancy planning. CONCLUSIONS: No differences in DOR, measured by levels of AMH, were observed between pwMS MS and HF in Chile. As expected, AMH levels were correlated only with ageing. This information may be evaluated early during the disease course to help patients and neurologists with fertility counselling and family planning considerations regarding DMT use.

Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) in Chile: lessons learned from challenging cases.

BACKGROUND: Anti-Myelin Oligodendrocyte Glycoprotein (MOG) Antibody Associated Disease (MOGAD) is an emerging disorder recognized as a clinical entity distinct from Multiple Sclerosis and Aquaporin-4-positive Neuromyelitis Optica Spectrum Disorders (NMOSD-AQP4+), and its phenotypic spectrum continues to expand. Most information about its clinical course has emerged from retrospective studies, and treatment response both in acute and chronic-relapsing disease is still limited. We aimed to describe the clinical and paraclinical characteristics of monophasic and relapsing, paediatric and adult patients with MOGAD under regular clinical care in Chile, highlighting some challenging cases that are far from being considered benign. METHODS: Observational, retrospective, and prospective longitudinal multicentre study including patients with positive serum MOG-IgG assessed by cell-based assay. RESULTS: We include 35 patients, 71% women, median age at onset 30 years (range 1-68), 23% had paediatric onset, with a median disease-duration 24 months (range 12-348). In the whole cohort, the most frequent symptoms at onset were isolated optic neuritis (ON) (34%) and myelitis (22%). Encephalitis with seizures or encephalomyelitis was the most common presentation in paediatric-onset patients 75% (n = 6), compared to 11% (n = 3) of the adult-onset patients (p < 0.001). A relapsing course was observed in 34%, these patients were younger (25 vs. 34 years, p = 0.004) and with a longer disease duration (64 vs. 6 months, p = 0.004) compared to monophasic patients. Two patients developed encephalitis with seizures/status epilepticus, with concomitant positive CSF anti-NMDAR-IgG. Chronic immunotherapy was ever prescribed in 77%, the most frequent was rituximab (35%). Relapses under chronic immunotherapy occurred in 5/27 patients (18.5%), two of them under rituximab, one paediatric patient who started combined therapy with monthly IVIG and one adult patient that switched to satralizumab plus mycophenolate. The median EDSS at the last follow-up was 1.5 (range 0-6.0). CONCLUSION: In Chile, patients with MOGAD exhibit a wide spectrum of clinical presentations at disease onset and during relapses. Close monitoring is needed, particularly in younger patients with short follow-up periods.

The content and effects of trunk rehabilitation on trunk and upper limb performance in people with multiple sclerosis: a systematic review.

INTRODUCTION: Persons with multiple sclerosis (pwMS) could have an impaired trunk and reduced postural control, which negatively impacts activities of daily living. Evidence is growing to consider the positive effects of trunk training on fall incidence and balance problems. Effects on trunk and upper limb performance is unknown. This systematic review provides an overview of trunk training programs and their effects in MS, specifically focusing on the content of training modalities and the effects on trunk and upper limb performance. EVIDENCE ACQUISITION: Two electronic databases were used: PubMed and Web Of Science (WOS). Intervention studies (with- and without control group) published in English, investigating the effects of active trunk training on trunk and upper limb performance in pwMS, were included. EVIDENCE SYNTHESIS: Sixteen studies met the criteria, investigating different rehabilitation modalities. The included interventions in the review varied between more generic postural interventions such as Pilates (N.=8) and Ai Chi (N.=1), with a focus on abdominal muscle activation, breathing, neutral position and lower extremity movements. Further, specifically developed trunk training programs like GroupCoreDIST/ SIT / CoDuSe (N.=6) and Bobath based trunk training (N.=1) are detected, with the main focus on trunk strengthening and dynamic movements. An overall improvement in trunk performance was reported in several tests on trunk strength, stability and coordination. While the majority of the programs integrated the upper limb, only half of them used upper limb outcome measures to evaluate the effect. Here, overall significant improvements were found for the upper limb. CONCLUSIONS: This systematic review showed that different types of trunk training programs can improve trunk and upper limb function in PwMS. The findings of this review suggest that a focus on trunk training to achieve effects on upper limb is reasonable. Future research is needed to further explore relations and the effect sizes.

Safety and humoral response rate of inactivated and mRNA vaccines against SARS-CoV-2 in patients with Multiple Sclerosis.

BACKGROUND: Safety and effectiveness outcomes in Multiple Sclerosis (MS) patients receiving different disease-modifying therapies (DMT) and different types of vaccines against SARS-CoV-2 are limited. Growing evidence coming mainly from Israel, Europe and North America using mRNA and adenoviral vector vaccines has been published. OBJECTIVES: To assess the safety and humoral response of inactivated virus and mRNA vaccines against SARS-CoV-2 in patients with MS. METHODS: Ongoing, multicentric, prospective, observational study performed between February and September 2021. Humoral response (antibodies against spike-1 protein) was determined at least 4 weeks after the complete schedule of anti-SARS-CoV-2 vaccines. Categorical outcome (positive/negative) and total antibody titres were recorded. Adverse events supposedly attributable to vaccination (AESAV) were collected. RESULTS: 178 patients, 68% women, mean age 39.7 ± 11.2 years, 123 received inactivated (Coronavac-Sinovac), 51 mRNA (Pfizer-BioNtech), and 4 adenoviral vector vaccines (CanSino n = 2, Jonhson&Johnson-Jannsen n = 1, Oxford-AstraZeneca n = 1). Six patients had a history of COVID-19 before vaccination. Overall humoral response was observed in 66.9% (62.6% inactivated vs. 78.4% mRNA, p = 0.04). Positive anti-S1-antibodies were observed in 100% of patients with no DMT (n = 3), 100% with interferon/glatiramer-acetate (n = 11), 100% with teriflunomide/dimethyl-fumarate (n = 16), 100% with natalizumab (n = 10), 100% with alemtuzumab (n = 8), 90% with cladribine (n = 10), and 88% with fingolimod (n = 17), while 43% of patients receiving antiCD20 (n = 99) were positive (38% inactivated vaccine vs. 59% mRNA vaccine, p = 0.05). In the multivariate analysis including antiCD20 patients, the predictors for a positive humoral response were receiving the mRNA vaccine (OR 8.11 (1.79-36.8), p = 0.007) and a lower number of total infusions (OR 0.44 (0.27-0.74) p = 0.002. The most frequent AESAV was local pain (14%), with 4 (2.2%) patients experiencing mild-moderate relapses within 8 weeks of first vaccination compared to 11 relapses (6.2%) within the 8 weeks before vaccination (Chi-squared 3.41, p = 0.06). DISCUSSION: A higher humoral response rate was observed using the mRNA compared to the inactivated vaccine, while patients using antiCD20 had a significantly lower response rate, and patients using antiCD20 and fingolimod had lower antibody titres. In this MS patient cohort, inactivated and mRNA vaccines against SARS-CoV-2 appear to be safe, with no increase in relapse rate. This information may help guidelines including booster shots and types of vaccines in selected populations.

Systematic evaluation of the guidelines for rehabilitation in multiple sclerosis patients: an overview according to ICF functioning domains.

High-quality clinical practice guidelines (CPGs) can provide evidence-based recommendations for optimizing care on managing multiple sclerosis (MS). There is currently no review that compiles recommendations of high-quality CPGs to guide decision-making for MS rehabilitation. The aim was to identify evidence-based recommendations in high-quality multidisciplinary English CPGs for rehabilitation in MS. CPGs published in the last 10 years (2009-2019) that described recommendations on rehabilitation were searched in PubMed, Turning Research into Practice database, International Guideline databases, National Guideline databases and websites of MS organizations. Quality assessment of CPGs was conducted by two evaluators using the Appraisal of Guidelines for Research and Evaluation II instrument. Recommendations were classified according to the International Classification of Functioning, Disability and Health (ICF) and the International Classification of Health Intervention (ICHI) and documented in terms of strength of recommendation and level of evidence. Five CPGs satisfied the inclusion criteria. Of 120 recommendations, 38 had a strong level with moderate to low level of evidence, 61 were of weak strength and 18 were formulated by the consensus of experts. Recommendations were categorized into 12 domains and 1 chapter on the body function level, 1 chapter on activity level and 2 domains on external factors. The existing CPGs demonstrated more than 100 evidence level recommendations to be followed at the clinical practice, most in body functions of the ICF. Developing up-to-date CPGs with more focus on activity and participation domains for countries with various healthcare backgrounds may be useful for a best clinical practice.

Pregnancy outcomes in women with Multiple Sclerosis.

INTRODUCTION: Women represent two-thirds of the MS population and are usually diagnosed during childbearing age. Collection of local information about pregnancy outcomes is fundamental to support individual decision-making. OBJECTIVE: To explore the trends in pregnancy decision making and pregnancy outcomes before (PreMS) and after (PostMS) MS diagnosis. METHODS: We developed a questionnaire for retrospective assessment of pregnancy outcomes in PreMS and PostMS patients under regular care at the Programa de Esclerosis Multiple UC in Chile. RESULTS: From the 218 women who responded to the questionnaire, 67 women did not have pregnancies. The total number of pregnancies registered was 299, 223 were PreMS (97 women, mean 2.5 ± 1.3 per/woman), and 76 PostMS (59 women, mean 1.9 ± 1.1 per/woman, p = 0.003). Mean age at first pregnancy was 27.6 ± 6.2 in PreMS, and 32.6 ± 4.6 years in PostMS women (p < 0.001). Significant differences between PreMS and PostMS pregnancy outcomes were cesarean section (37% vs. 66%; OR 2.74 95%CI(1.5-52), p=0.002), suspected relapse during 6 months after birth (7% vs. 18%, p<0.001), and breastfeeding (83% vs 67%, p=0.005). Gestational age, weight/size at birth, were not different between groups. Major malformations were observed similarly in both groups. CONCLUSIONS: Changes in pregnancy decision-making after MS diagnosis occur, having fewer children and at an older age. It also changes obstetrician decisions for cesarean sections, with a 3 fold increase. Regarding newborn outcomes, there were no differences between groups.

Clinical assessment, management, and rehabilitation of walking impairment in MS: an expert review.

INTRODUCTION: One of the most common and life-altering consequences of Multiple Sclerosis (MS) is walking impairment. The distance, speed, and Gait pattern functions are components of the International Classification of Functioning, Disability, and Health (ICF) and are also predictors of dependency in terms of daily living activities in patients with MS (pwMS). AREAS COVERED: This article provides an overview of walking impairment in pwMS, with focus on the assessment of gait and the rehabilitation approaches. EXPERT OPINION: The authors recommend that pwMS undergo gait assessment integrating the ICF perspective using validated clinical outcome measures that cover spatiotemporal gait parameters. Moreover, assessment of walking speed with short walking capacity tests such as the timed 25-foot walk (T25FW) or the 10-m walk test (10 MWT) and tests for walking distance with middle distance tests such as the 2-min walk test (2MWT) and the 6-min walk test (6MWT). This review further highlights strategies that may restore walking function including pharmacological symptomatic treatment and non-pharmacological rehabilitation approaches such as exercise and task-specific training providing an appraisal of mobility targeted therapies to be considered when planning multidisciplinary comprehensive-care of pwMS. Finally, new and novel strategies such as motor imagery and rhythmic auditory stimulation have been developed to improve walking speed and distance in pwMS.

Multiple sclerosis and related disorders: Short report peripheral vascular events in a real-world cohort of multiple sclerosis patients using Fingolimod.

BACKGROUND: Fingolimod is a high-efficacy disease-modifying therapy for multiple sclerosis (MS) and was the first oral treatment approved for the disease. Adverse events include bradyarrhythmia, hypertension, macular oedema and increased risk of infections, mainly due to its main mechanism of action, the non-selective modulation of sphingosine-1-phosphate receptor. METHODS AND RESULTS: We report the baseline characteristics, effectiveness outcomes and adverse events of a prospective cohort of 177 patients with a median treatment duration of 24 months, in which four patients (2.3%) presented with otherwise non-provoked peripheral vascular events (PVE). CONCLUSIONS: Further studies are still needed to evaluate the frequency and severity of PVE in fingolimod patients.

Prevalence of comorbidities in Multiple Sclerosis and impact on physical disability according to disease phenotypes.

BACKGROUND: Comorbidities are prevalent among Multiple Sclerosis (MS) patients. Few studies have characterized their prevalence and impact in Latin American populations. OBJECTIVE: We aim to assess the prevalence of comorbidities and their impact on the risk of physical disability across different MS phenotypes. METHODS: Cross-sectional multicenter study of patients under regular clinical care at the Programa de Esclerosis Múltiple UC and Hospital Dr. Sótero del Río in Chile. Prevalence of comorbidities was estimated from the retrospective assessment of electronic medical charts. Disease phenotypes were categorized into two groups: clinically isolated syndrome/relapsing-remitting (inflammatory group) and primary/secondary progressive MS patients (progressive group). A multivariable analysis using binary logistic regression for assessing the risk of EDSS ≥ 6.0 in each group was performed. RESULTS: A total of 453 patients was included, 71% female, mean age at onset 31 years, mean disease duration 10 years, and median EDSS 2.0 (range 0-10). In the whole sample, most prevalent comorbidities were ever-smoking (42.2%), depression/anxiety (34.9%), thyroid disease (15.7%), hypertension (11.3%) and insulin resistance/type 2 diabetes mellitus (11.0%). When assessing the risk of EDSS ≥ 6, in the inflammatory group (N = 366), age at onset (OR 1.06, 95%CI(1.02-1.11), p = 0.008), disease duration (OR 1.06, 95%CI(1.00-1.12), p = 0.039) and epilepsy comorbidity (OR 5.36, 95%CI(1.33-21.5), p = 0.018) were associated with a higher risk of disability. In the progressive group (N = 87), disease duration was a risk factor (OR 1.08 95%CI(1.02-1.16), p = 0.014), while shorter diagnostic delay (OR 0.91 95%CI(0.85-0.99), p = 0.025) and insulin resistance/type 2 diabetes mellitus comorbidity were protective factors (OR 0.18 95%CI(0.04-0.83), p = 0.028), 72% of these patients were receiving metformin. CONCLUSIONS: Comorbidities are common across different MS disease phenotypes. Epilepsy seems particularly related with a higher risk of physical disability in relapsing-remitting patients, while the role of insulin resistance/type 2 diabetes mellitus or the impact of metformin use as a protective factor should be further studied. Prospective and larger studies are still needed in order to assess the real impact of comorbidities and their management in MS outcomes.

[Stem cells therapy in amyotrophic lateral sclerosis treatment. A critical view]. / Trasplante de células troncales como terapia para la esclerosis lateral amiotrófica. Una mirada crítica.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. At present, there are not curative therapies for ALS. Pathogenic and progression mechanisms suggest the existence of oxidative stress, abnormal intracellular protein aggregation, mitochondrial dysfunction, axonal transport impairment, impairment of trophic support, altered glial cell function, and glutamate excitoxicity. AIM: To evaluate therapeutic results with adult stem cell for ALS treatment. DEVELOPMENT: Stem cells represent a potential therapeutic strategy, because their biological mechanisms could act on several of the pathogenic mechanisms proposed for ALS. Bone marrow mesenchymal stem cells are especially interesting among adult stem cells. Mesenchymal stem cells can differentiate in all central nervous system cells and potentially replace them. Furthermore, they have immunomodulatory effects, secreting, especially in neuroinflammatory environments, neurotrophic and antiinflammatory factors. Studies in murine models of ALS show decrease of inflammation and disease progression, and increase on animal highly heterogeneous, suggest that mesenchymal stem cells transplant in ALS appears to be safe. However, they fail showing clinical improvement of patients. CONCLUSION: Additional preclinical studies are necessary to refine this therapeutic approach, to assess long term survival and differentiation of mesenchymal stem cells, dosing, biological activity and safety should be conducted before any planning further human testing occurs.

[Limbic encephalitis associated to voltage dependent potassium channel antibodies: report of one case]. / Encefalitis límbica por anticuerpos anticanales de potasio dependientes de voltaje: Caso clínico.

Limbic encephalitis (LE) can be associated to cancer, viral infection or be idiopathic. One form is associated to voltage dependent potassium channel (VKC) antibodies. The clinical presentation includes impairment of consciousness, amnesia and temporal lobe seizures; typical abnormalities are also found in brain magnetic resonance. We report a 68 year-old male who had LE associated to VKC antibodies. The patient was treated with steroids with a partial response. At the moment of the report he is asymptomatic and continues with prednisone treatment .

[Treatment of refractory status epilepticus with topiramate. Report of three cases]. / Tratamiento del estado epiléptico refractario con topiramato oral.

Refractory status epilepticus is a catastrophic illness of the central nervous system, with a mortality rate that reaches 50%. We report three patients admitted with refractory status epilepticus: a 24 year-old male that discontinued antiepileptic medications, a 46 year-old male with a focal epilepsy secondary to an encephalitis that discontinued medications due to gastrointestinal problems and a 59 year-old male with an ischemic encephalopathy AH were treated with topiramate, delivered through a nasogastric tube with a good response.

Trasplante de células troncales: mecanismos de acción para sus usos potenciales en neurología / Stem cells transplant: potentially useful mechanism for neurology

Stem cells have a great potential for the treatment of presently incurable neurological diseases, including spinal trauma, cerebrovascular pathology, brain tumor and neurodegenerative processes, such as Parkinson and Alzheimer's disease, Huntington, multiple sclerosis and amyotrophic lateral sclerosis. Aims: To discuss the characteristics of the various stem cells types having been proposed for cell therapy, and the biological mechanisms responsible for their therapeutic effects. Report: Stem cells can be induced to differentiate into specialized cells such as neurons and glial cells, and they can influence the environment around them, both through the secretion of neurotrophic factors and immunomodulation of the host neuroimmune response. Furthermore, the understanding of the modulatory effect of stem cells could lead to the development of new therapeutic paradigms. Nevertheless, two important limitations of the field are that the ideal source for stem cells is not well defined yet and the mechanism of stem cell mediated functional improvement is not well understood. Conclusions: Research is currently focused on the biological mechanisms of stem cells therapy and the assessment of stem cell programming and delivery to the target regions. Furthermore, future research will increasingly target ways to enhance effectiveness of the stem cell therapy, including its combination with gene therapy. Regardless its enormous potentials, there are still many problems to be solved before clinical application of stem cell therapy can de used in neurological disease patients.

Introducción: Las células troncales tienen un gran potencial para el tratamiento de enfermedades neurológicas actualmente incurables, incluyendo el trauma espinal, patología cerebrovascular y procesos neurodegenerativos como el Parkinson, Alzheimer, Huntington, esclerosis múltiple o la esclerosis lateral amiotrófica. Objetivo: Discutir las características de diversas células troncales que han sido propuestas para terapia celular, y los mecanismos biológicos responsables de sus efectos terapéuticos. Desarrollo: Las células troncales pueden ser inducidas a diferenciarse en células especializadas como neuronas y células gliales, y pueden influenciar su entorno, tanto a través de la secreción de factores neurotróficos como por la inmunomodulación de la respuesta neuroinmune. La comprensión del efecto modulador de las células troncales podría orientar el desarrollo de nuevos paradigmas terapéuticos. Sin embargo, dos limitaciones importantes que persisten son, que la célula troncal ideal aún no está bien definida, y que los mecanismos que median la mejoría inducida por ellas no se comprende bien. Conclusiones: La investigación se enfoca actualmente en los mecanismos biológicos de la actividad terapéutica de las células troncales, en la evaluación de la programación celular y en su acceso a las regiones blanco. La investigación futura se dirigirá progresivamente a encontrar formas de aumentar la efectividad de las células troncales, incluyendo su combinación con terapia genética. Sin embargo, aún existen numerosos problemas que resolver antes que la terapia con células troncales pueda ser usada en pacientes con enfermedades neurológicas.

Encefalitis límbica por anticuerpos anticanales de potasio dependientes de voltaje: caso clínico / Limbic encephalitis associated to voltage dependent potassium channel antibodies: report of one case

Limbic encephalitis (LE) can be associated to cancer, viral infection or be idiopathic. One form is associated to voltage dependent potassium channel (VKC) antibodies. The clinical presentation includes impairment of consciousness, amnesia and temporal lobe seizures; typical abnormalities are also found in brain magnetic resonance. We report a 68 year-old male who had LE associated to VKC antibodies. The patient was treated with steroids with a partial response. At the moment of the report he is asymptomatic and continues with prednisone treatment.

Tratamiento del estado epiléptico refractario con topiramato oral / Treatment of refractory status epilepticus with topiramate: report of three cases

Refractory status epilepticus is a catastrophic illness of the central nervous system, with a mortality rate that reaches 50 percent. We report three patients admitted with refractory status epilepticus: a 24 year-old male that discontinued antiepileptic medications, a 46 year-old male with a focal epilepsy secondary to an encephalitis that discontinued medications due to gastrointestinal problems and a 59 year-old male with an ischemic encephalopathy AH were treated with topiramate, delivered through a nasogastric tube with a good response.

Estudio y evaluación en niños con episodios recurrentes de rinosinusitis / Study and evaluation in children with recurrent rhinosinusitis

La Rinosinusitis (RS) es una patología frecuente en la población pediátrica. Anualmente un niño cursa aproximadamente 6 a 8 episodios de infecciones respiratorias altas de origen viral, de éstos, entre 5-13 por ciento se complican con una RS bacteriana. El diagnóstico del episodio agudo es esencialmente clínico. Se define RS recurrente a la presencia de 3 o más episodios de RS en 6 meses o 4 en un año con periodos libre de sintomatología entre los episodios. Estos niños requieren un manejo especial, basado en tratamiento antibiótico de segunda línea junto a la certificación con imágenes de la resolución del cuadro. Pasado el episodio agudo, es esencial realizar estudio de factores predisponentes, buscando causas potencialmente modificables, lo que conjuntamente con derivación oportuna al especialista determinará el manejo futuro.