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1.
Wiad Lek ; 74(2): 367-370, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33813502

RESUMEN

The aim was to analyze the contemporary scientific literature on Devic's opticomyelitis and to present a case report from our clinical practice. Based on the patient's complaints, case history and features of clinical course, objective neurological status, clinical laboratory and additional examination methods, characteristic MR-patterns, consultations of related specialists and differential diagnostics, we made the clinical diagnosis according to ICD-10: G36.0 Devic's opticomyelitis, exacerbation, with a sustained bilateral lesion of the optic nerves in the form of retrobulbar neuritis with the development of partial atrophy of the optic nerves in both eyes, spinal cord lesions with common cystic, cicatrical and atrophic alterations at C1-Th8 level with moderate lower paraparesis, expressed by sensory ataxia, sensory disturbances by the descending conductive type from Th10, impaired function of pelvic organs by the type of acute urinary retention, asthenic and neurotic syndrome. Widespread cases of demyelinating pathology in medical practice and complexity of differential diagnostics determine the need for a specific diagnostic algorithm. This algorithm should consider anamnestic data along with the course of the disease, clinical, laboratory and instrumental examination, including neuroimaging, analysis of CSF for oligoclonal bands, analysis for IgG antibodies to AQP4, which will allow to carry out diagnostics and to decide on tactics for further management of patients of this cohort. Further research is needed to conduct additional studies for optimization of tactics for dynamics monitoring and improvement of diagnostic, treatment and rehabilitation measures in patients with Devic's opticomyelitis, including appropriate immunological control, given the complexity of differential diagnostics and the affinity of this pathology to multiple sclerosis.


Asunto(s)
Esclerosis Múltiple , Neuromielitis Óptica , Atrofia , Diagnóstico Diferencial , Humanos , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/diagnóstico , Neuromielitis Óptica/diagnóstico
2.
Medicine (Baltimore) ; 100(9): e24931, 2021 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-33655958

RESUMEN

ABSTRACT: Although the mutual relationship between ambulation and physical activity (PA) in people with multiple sclerosis (pwMS) has been described in several studies, there is still a lack of detailed information about the way in which specific aspects of the gait cycle are associated with amount and intensity of PA. This study aimed to verify the existence of possible relationships among PA parameters and the spatio-temporal parameters of gait when both are instrumentally assessed.Thirty-one pwMS (17F, 14 M, mean age 52.5, mean Expanded Disability Status Scale (EDSS) score 3.1) were requested to wear a tri-axial accelerometer 24 hours/day for 7 consecutive days and underwent an instrumental gait analysis, performed using an inertial sensor located on the low back, immediately before the PA assessment period. Main spatio-temporal parameters of gait (i.e., gait speed, stride length, cadence and duration of stance, swing, and double support phase) were extracted by processing trunk accelerations. PA was quantified using average number of daily steps and percentage of time spent at different PA intensity, the latter calculated using cut-point sets previously validated for MS. The existence of possible relationships between PA and gait parameters was assessed using Spearman rank correlation coefficient rho.Gait speed and stride length were the parameters with the highest number of significant correlations with PA features. In particular, they were found moderately to largely correlated with number of daily steps (rho 0.62, P< .001), percentage of sedentary activity (rho = -0.44, P < .001) and percentage of moderate-to-vigorous activity (rho = 0.48, P < .001). Small to moderate significant correlations were observed between PA intensity and duration of stance, swing and double support phases.The data obtained suggest that the most relevant determinants associated with higher and more intense levels of PA in free-living conditions are gait speed and stride length. The simultaneous quantitative assessment of gait parameters and PA levels might represent a useful support for physical therapists in tailoring optimized rehabilitative and training interventions.


Asunto(s)
Ejercicio Físico/fisiología , Trastornos Neurológicos de la Marcha/fisiopatología , Marcha/fisiología , Esclerosis Múltiple/complicaciones , Modalidades de Fisioterapia , Adolescente , Adulto , Anciano , Femenino , Estudios de Seguimiento , Análisis de la Marcha , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/rehabilitación , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/fisiopatología , Esclerosis Múltiple/rehabilitación , Estudios Retrospectivos , Adulto Joven
3.
Evid Based Dent ; 22(1): 44-45, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33772137

RESUMEN

Data sources PubMed, Scopus, Web of Science, MEDLINE and CINAHL.Study selection Randomised controlled trials, cross-sectional studies and cohort studies.Data extraction and synthesis Two reviewers independently extracted data using piloted forms and contacted authors if relevant data were missing. Assessment of quality was done using the Newcastle-Ottawa scale (NOS) for both cohort and cross-sectional studies. The score of NOS ranged from 1-9, where 6-7 is considered moderate quality while 8-9 is high quality.Results Seventeen studies were included in the review (13 cross-sectional and four cohort). Seven out of 13 cross-sectional studies scored ≤5 which indicates poor quality. The four case-control studies were of moderate quality. Overall, there is limited evidence that patients with multiple sclerosis (MS) have more dental caries or gingival disease. However, evidence suggests that patients with MS have more risk of periodontal disease and poor oral hygiene. The evidence also suggests a moderate association between MS and temporomandibular disorders (TMD).Conclusions With the exception of TMD, current evidence does not establish an association between MS and most oral health conditions. More high-quality evidence is needed to further explore and establish an association.


Asunto(s)
Caries Dental , Esclerosis Múltiple , Estudios Transversales , Caries Dental/epidemiología , Humanos , Esclerosis Múltiple/complicaciones , Salud Bucal , Higiene Bucal
4.
Int J Mol Sci ; 22(4)2021 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-33670394

RESUMEN

The novel coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a global challenge. Currently, there is some information on the consequences of COVID-19 infection in multiple sclerosis (MS) patients, as it is a newly discovered coronavirus, but its far-reaching effects on participation in neurodegenerative diseases seem to be significant. Recent cases reports showed that SARS-CoV-2 may be responsible for initiating the demyelination process in people who previously had no symptoms associated with any nervous system disorders. It is presently known that infection of SARS-CoV-2 evokes cytokine storm syndrome, which may be one of the factors leading to the acute cerebrovascular disease. One of the substantial problems is the coexistence of cerebrovascular disease and MS in an individual's life span. Epidemiological studies showed an enhanced risk of death rate from vascular disabilities in MS patients of approximately 30%. It has been demonstrated that patients with severe SARS-CoV-2 infection usually show increased levels of D-dimer, fibrinogen, C-reactive protein (CRP), and overactivation of blood platelets, which are essential elements of prothrombotic events. In this review, the latest knowledge gathered during an ongoing pandemic of SARS-CoV-2 infection on the neurodegeneration processes in MS is discussed.


Asunto(s)
/complicaciones , Esclerosis Múltiple/complicaciones , Enfermedades Neurodegenerativas/etiología , Animales , /virología , Síndrome de Liberación de Citoquinas/etiología , Síndrome de Liberación de Citoquinas/patología , Síndrome de Liberación de Citoquinas/virología , Humanos , Esclerosis Múltiple/patología , Esclerosis Múltiple/virología , Enfermedades Neurodegenerativas/patología , Enfermedades Neurodegenerativas/virología , Trombosis/etiología , Trombosis/patología
5.
Arq Neuropsiquiatr ; 79(1): 44-50, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33656111

RESUMEN

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disease that affects the central nervous system. The impact of MS transcends physical functions and extends to psychological impairment. Approximately 50% of people with MS develop depressive symptoms during their lifetime and depressive symptoms may predict impairment of physical functions. However, prediction of depressive symptoms based on objective measures of physical functions is still necessary. OBJECTIVE: To compare physical functions between people with MS presenting depressive symptoms or not and to identify predictors of depressive symptoms using objective measures of physical functions. METHODS: Cross-sectional study including 26 people with MS. Anxiety and/or depressive symptoms were assessed by the Beck Depression Inventory-II (BDI-II) and by the Hospital Anxiety and Depression Scale (HADS). Outcomes of physical functions included: the Nnnine-hole Ppeg Ttest (NHPT), knee muscle strength, balance control, the Timed Up and Go Test (TUG), and the 6-minute walk test (6MWT). Perceived exertion was measured using the Borg scale. RESULTS: The frequency of depressive symptoms was 42% in people with MS. Balance control during a more challenging task was impaired in people with MS who presented depressive symptoms. Balance could explain 21-24% of the variance in depressive symptoms. 6MWT and TUG presented a trend of significance explaining 16% of the variance in the BDI-II score. CONCLUSIONS: Impairment in physical functions consists in a potential predictor of depressive symptoms in people with MS. Exercise interventions aiming at the improvement of physical functions, together with the treatment of depressive symptoms and conventional medical treatment, are suggested.


Asunto(s)
Depresión , Esclerosis Múltiple , Estudios Transversales , Depresión/etiología , Humanos , Esclerosis Múltiple/complicaciones , Equilibrio Postural , Estudios de Tiempo y Movimiento
6.
Eur J Radiol ; 137: 109610, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33657474

RESUMEN

PURPOSE: Fatigue is a common symptom in patients with multiple sclerosis (MS) with unknown pathophysiology. Dysfunction of the GABAergic/glutamatergic pathways involving inhibitory and excitatory neurotransmitters such as  γ-aminobutyric acid (GABA) and glutamine + glutamate pool (Glx) have been implicated in several neurological disorders. This study is aimed to evaluate the potential role of GABA and Glx in the origin of central fatigue in relapse remitting MS (RRMS) patients. METHODS: 24 RRMS patients and 16 age- and sex-matched healthy controls (HC) were scanned using Mescher-Garwood point resolved spectroscopy (MEGA-PRESS) with a 3 T system to quantify GABA+ and Glx from prefrontal (PFC) and sensorimotor (SMC) cortices. Self-reported fatigue status was measured on all participants using the Modified Fatigue Impact Scale (MFIS). RESULTS: RRMS patients had higher fatigue scores relative to HC (p ≤  0.05). Compared to HC, Glx levels in RRMS patients were significantly decreased in SMC (p =  0.04). Significant correlations were found between fatigue scores and GABA+ (r = -0.531, p =  0.008) and Glx (r = 0.511, p =  0.018) in PFC. Physical fatigue was negatively correlated with GABA+ in SMC and PFC (r = -0.428 and -0.472 respectively, p ≤  0.04) and positively with PFC Glx (r = 0.480, p =  0.028). CONCLUSION: The associations between fatigue and GABA + and Glx suggest that there might be dysregulation of GABAergic/glutamatergic neurotransmission in the pathophysiological mechanism of central fatigue in MS.


Asunto(s)
Ácido Glutámico , Esclerosis Múltiple , Encéfalo/diagnóstico por imagen , Fatiga , Glutamina , Humanos , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/diagnóstico por imagen , Ácido gamma-Aminobutírico
7.
Int J Mol Sci ; 22(5)2021 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-33669083

RESUMEN

Phelan McDermid syndrome (PMcD) is a neurogenetic disease associated with haploinsufficiency of the SHANK3 gene due to a spectrum of anomalies in the terminal region of the long arm of chromosome 22. SHANK3 is the abbreviation for SH3 domain and ankyrin repeat-containing protein, a gene that encodes for proteins of the postsynaptic density (PSD) of excitatory synapses. This PSD is relevant for the induction and plasticity of spine and synapse formation as a basis for learning processes and long-term potentiation. Individuals with PMcD present with intellectual disability, muscular hypotonia, and severely delayed or absent speech. Further neuropsychiatric manifestations cover symptoms of the autism spectrum, epilepsy, bipolar disorders, schizophrenia, and regression. Regression is one of the most feared syndromes by relatives of PMcD patients. Current scientific evidence indicates that the onset of regression is variable and affects language, motor skills, activities of daily living and cognition. In the case of regression, patients normally undergo further diagnostics to exclude treatable reasons such as complex-focal seizures or psychiatric comorbidities. Here, we report, for the first time, the case of a young female who developed progressive symptoms of regression and a dystonic-spastic hemiparesis that could be traced back to a comorbid multiple sclerosis and that improved after treatment with methylprednisolone.


Asunto(s)
Enfermedades Autoinmunes/tratamiento farmacológico , Trastornos de los Cromosomas/complicaciones , Metilprednisolona/administración & dosificación , Esclerosis Múltiple/complicaciones , Regresión Psicológica , Anomalías Múltiples/genética , Anomalías Múltiples/fisiopatología , Administración Intravenosa , Adulto , Trastorno del Espectro Autista/complicaciones , Enfermedades Autoinmunes/líquido cefalorraquídeo , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/inmunología , Deleción Cromosómica , Trastornos de los Cromosomas/líquido cefalorraquídeo , Trastornos de los Cromosomas/diagnóstico por imagen , Trastornos de los Cromosomas/genética , Cromosomas Humanos 21-22 e Y/genética , Cromosomas Humanos Par 22/genética , Femenino , Humanos , Imagen por Resonancia Magnética , Esclerosis Múltiple/líquido cefalorraquídeo , Proteínas del Tejido Nervioso/genética , Eliminación de Secuencia , Punción Espinal
8.
Clin Neurol Neurosurg ; 203: 106563, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33631509

RESUMEN

BACKGROUND: Iran is one of the countries with a high prevalence of multiple sclerosis (MS) and COVID-19.MS patients receiving the immunomodulatory or immunosuppressive therapy have a higher risk of infection. Due to the significance of determining the risk factors for getting COVID-19 among MS patients, the present study was designed to assess the risk of infection following the pulse steroid therapy. METHODS: This cross-sectional study included all MS patients that received corticosteroids in Tehran from December 2019 to August 2020 during the COVID-19 pandemic spread. The subjects' clinical records including their sex, age, the type of MS, the type of medication, the number of days using corticosteroids, the status of prednisolone intake, and the number of days receiving prednisolone after the corticosteroid therapy were obtained. Moreover, main outcomes such as COVID-19 infection and the occurrence of death were recorded by patient's visits and follow-up phone calls. COVID-19 infection was confirmed by physicians according to the clinical performance of RT-PCR, chest CT scan, and antibody tests. RESULTS: Totally, 133 MS cases participated in the study, and the pulse therapy was completed for 104 (78.2%) patients up to 5-7 days. 89 (66.9%) cases used the prednisolone tablet following the pulse therapy. Overall, the infection by Covid-19 was observed in 8 (6%) cases, among whom 5 (71.4%) cases received the pulse therapy for 5-7 days and 4 (57.1%) cases had a history of taking the prednisolone tablet. The age of less than 40 years (OR = 1.03; 95% CI (0.23-4.51)), male sex (OR = 0.35; 95% CI (0.03-3.34)), and the RRMS type (OR = 2.87; 95% CI (0.52-15.72)) had no effect on the risk of Covid-19 infection. In addition, there was not statistically significant difference between subjects with the short-term pulse therapy duration (3-4 days) (OR 0.68 (0.12-3.74) and those with the long-term pulse therapy duration (5-7 days). Similarly, no statistically significant difference was observed between subjects taking prednisolone (OR = 1.62 (0.34-7.61) and those not taking prednisolone. Furthermore, there was no significant association between different medication groups and the risk of Covid-19 infection (p < 0.05). No death occurred due to Covid-19 infection among the subjects. CONCLUSION: COVID-19 infection was more common among female and younger patients as well as patients with a longer duration of the pulse therapy and prednisolone intake. There was no significant association between the pulse steroid therapy in MS patients and the risk of infection by COVID-19 in the Iranian population.


Asunto(s)
Corticoesteroides/administración & dosificación , Esclerosis Múltiple/tratamiento farmacológico , Adulto , Antiinflamatorios/administración & dosificación , Estudios Transversales , Femenino , Humanos , Irán , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/complicaciones , Prednisolona/administración & dosificación , Quimioterapia por Pulso
9.
Fortschr Neurol Psychiatr ; 89(4): 168-177, 2021 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-33571999

RESUMEN

BACKGROUND: It is estimated that 240,000 people suffer from multiple sclerosis in Germany. In addition to sensory, motor, vegetative, and neuropsychological functional deficits, dysphagia is a highly relevant and disabling, although not well studied symptom of MS. OBJECTIVES: The purpose of this article is to provide an overview of the scientific background, increase awareness of the symptoms of dysphagia, and to introduce diagnostic tools for its management, overall aiming at alleviating symptoms of dysphagia in persons with MS, and improving their quality of life. METHODS: A structured literature review was conducted of what is currently known on the development, manifestation, diagnosis and treatment options for MS-related dysphagia. Due to the lack of class 1 evidence, in particular for diagnosis and treatment options of dysphagia, also smaller studies or pilot projects were included and discussed in this review. RESULTS: Data from imaging methods such as Flexible Endoscopic Evaluation of Swallowing and Videofluoroscopic Swallowing Evaluation enabled the diagnosis. There was a high variablity in the reported frequency of dysphagia in published studies, largely related to differences in methodology to evaluate the swallowing (from 38 % up to 81 %). Overall, dysphagia as a symptom of multiple sclerosis was underestimated at the patient and the physician level. According to current data from the German MS register, specific treatments were only carried out in 30% of the affected patients.


Asunto(s)
Trastornos de Deglución , Esclerosis Múltiple , Deglución , Trastornos de Deglución/diagnóstico , Trastornos de Deglución/etiología , Alemania/epidemiología , Humanos , Esclerosis Múltiple/complicaciones , Calidad de Vida
10.
Mutat Res ; 861-862: 503278, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33551096

RESUMEN

Multiple sclerosis (MS), a disease in which the immune system attacks nerve cells, has been associated with both genetic and environmental risk factors. We observed increased micronucleus (MN) formation in SJL/J mouse experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Most of these MN were due to chromosomal loss. Increased activation of MAP kinases, which leads to disruption of the mitotic spindle and improper segregation of chromosomes, is associated with MS. MAP kinase inhibitors, such as PD98059, may therefore be beneficial for MS. In the EAE model, PD98059 treatment reduced adverse effects, including MN formation, lipid peroxidation, and GSH oxidation. Interventions that mitigate chromosomal instability may have therapeutic value in MS.


Asunto(s)
Inestabilidad Cromosómica/efectos de los fármacos , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Flavonoides/farmacología , Proteínas Quinasas Activadas por Mitógenos/química , Esclerosis Múltiple/tratamiento farmacológico , Animales , Encefalomielitis Autoinmune Experimental/complicaciones , Encefalomielitis Autoinmune Experimental/patología , Femenino , Ratones , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/patología
11.
JAMA ; 325(8): 765-779, 2021 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-33620411

RESUMEN

Importance: Multiple sclerosis (MS) is an autoimmune-mediated neurodegenerative disease of the central nervous system characterized by inflammatory demyelination with axonal transection. MS affects an estimated 900 000 people in the US. MS typically presents in young adults (mean age of onset, 20-30 years) and can lead to physical disability, cognitive impairment, and decreased quality of life. This review summarizes current evidence regarding diagnosis and treatment of MS. Observations: MS typically presents in young adults aged 20 to 30 years with unilateral optic neuritis, partial myelitis, sensory disturbances, or brainstem syndromes such as internuclear ophthalmoplegia developing over several days. The prevalence of MS worldwide ranges from 5 to 300 per 100 000 people and increases at higher latitudes. Overall life expectancy is less than in the general population (75.9 vs 83.4 years), and MS more commonly affects women (female to male sex distribution of nearly 3:1). Diagnosis is made based on a combination of signs and symptoms, radiographic findings (eg, magnetic resonance imaging [MRI] T2 lesions), and laboratory findings (eg, cerebrospinal fluid-specific oligoclonal bands), which are components of the 2017 McDonald Criteria. Nine classes of disease-modifying therapies (DMTs), with varying mechanisms of action and routes of administration, are available for relapsing-remitting MS, defined as relapses at onset with stable neurologic disability between episodes, and secondary progressive MS with activity, defined as steadily increasing neurologic disability following a relapsing course with evidence of ongoing inflammatory activity. These drugs include interferons, glatiramer acetate, teriflunomide, sphingosine 1-phosphate receptor modulators, fumarates, cladribine, and 3 types of monoclonal antibodies. One additional DMT, ocrelizumab, is approved for primary progressive MS. These DMTs reduce clinical relapses and MRI lesions (new T2 lesions, gadolinium-enhancing lesions). Efficacy rates of current DMTs, defined by reduction in annualized relapse rates compared with placebo or active comparators, range from 29%-68%. Adverse effects include infections, bradycardia, heart blocks, macular edema, infusion reactions, injection-site reactions, and secondary autoimmune adverse effects, such as autoimmune thyroid disease. Conclusions and Relevance: MS is characterized by physical disability, cognitive impairment, and other symptoms that affect quality of life. Treatment with DMT can reduce the annual relapse rate by 29% to 68% compared with placebo or active comparator.


Asunto(s)
Inmunosupresores/uso terapéutico , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/tratamiento farmacológico , Sistema Nervioso Central/diagnóstico por imagen , Sistema Nervioso Central/patología , Trastornos del Conocimiento/etiología , Progresión de la Enfermedad , Fatiga/etiología , Femenino , Humanos , Imagen por Resonancia Magnética , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/fisiopatología , Embarazo , Calidad de Vida
12.
Mult Scler Relat Disord ; 49: 102754, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33609958

RESUMEN

BACKGROUND: Coronavirus disease 2019 (COVID-19) raises particular concerns for people with multiple sclerosis (PwMS) on disease-modifying treatments (DMTs), and for physicians caring for them. The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on PwMS receiving DMTs that inhibit immune cell trafficking, such as natalizumab (NTZ) and fingolimod (FTY), remains to be determined, as do the possible effects of these drugs on both the infection and the related disease. AIMS: To describe self-reported COVID-19 symptoms and disease severity in PwMS on NTZ or FTY who received serology confirmation of SARS-CoV-2 infection. METHODS: From 27th April to 3rd May 2020, telephone interviews were conducted with 140 PwMS under treatment with NTZ or FTY in order to collect structured data on multiple sclerosis (MS) and COVID-19. The patients, all followed at our center, were classified as symptomatic, paucisymptomatic or asymptomatic on the basis of their self-reported clinical characteristics. COVID-19 severity was rated on a 7-point ordinal scale. In addition, in the period 4th May to 3rd June 2020 SARS-CoV-2 serology testing, using the Roche SARS-CoV-2 IgG assay (ElecsysⓇ), was performed in 104/140 (74.2%) of the interviewed PwMS (50 treated with NTZ and 54 with FTY). RESULTS: 14/104 (13.4%) PwMS on NTZ or FTY had anti-SARS-CoV-2 antibodies: 8 met the criteria for asymptomatic, 3 for paucisymptomatic and 3 for symptomatic COVID-19 (COVID-19 severity score lower than 3). None of them required hospitalization or showed severe COVID-19 complications. CONCLUSIONS: Despite the relatively high SARS CoV-2 seroprevalence found in this sample of PwMS, all the positive cases showed either no or only mild COVID-19 symptoms. These reassuring findings indicate a lack of COVID-19 complications in PwMS on DMTs and support the hypothesis that it is safe to maintain ongoing treatment with these drugs in the current setting.


Asunto(s)
Anticuerpos Antivirales/sangre , Clorhidrato de Fingolimod/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Natalizumab/uso terapéutico , Adulto , Infecciones Asintomáticas , /inmunología , Femenino , Clorhidrato de Fingolimod/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/complicaciones , Natalizumab/efectos adversos , ARN Viral , Estudios Seroepidemiológicos
13.
Intern Med ; 60(1): 39-46, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33390470

RESUMEN

Objective Prospective memory (PM) is an important social cognitive function in everyday life. PM is one of the most affected cognitive domains in multiple sclerosis (MS) patients. Gray matter (GM) atrophy and plaques have been attracting attention for various cognitive impairments in MS patients. This study aimed to clarify the atrophic GM regions associated with PM deficits and investigate the relationship between the atrophic GM regions and GM plaques. Methods Twenty-one MS patients and 10 healthy controls (HCs) underwent neuropsychological tests and MRI. PM was assessed using subtests of the Rivermead Behavioural Memory Test. A lesion symptom analysis was performed using voxel-based morphometry (VBM). We then evaluated GM plaques in the corresponding areas using double inversion recovery (DIR). Results MS patients showed lower PM scores than HCs (p=0.0064). The GM volume of MS patients tended to be lower than those of HCs. VBM analyses revealed correlations of the PM score with the orbital part of the left inferior frontal gyrus, the left hippocampus, and the right parahippocampus. There was no GM plaque in the orbital part of the left inferior frontal gyrus and the right parahippocampus. Only one patient (4.8%) had GM plaque in the left hippocampus. Conclusion The left inferior frontal gyrus, the left hippocampus, and the right parahippocampus were associated with PM in MS, whereas these atrophic GM regions were not associated with GM plaque. Regardless of the location of plaques on DIR, both PM deficit and GM atrophy should be detected using neuropsychological tests and VBM in MS patients.


Asunto(s)
Memoria Episódica , Esclerosis Múltiple , Atrofia/patología , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Humanos , Imagen por Resonancia Magnética , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/diagnóstico por imagen
14.
J Stroke Cerebrovasc Dis ; 30(4): 105618, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33482571

RESUMEN

Recurrent episodes of neurological dysfunction and white matter lesions in a young adult raise suspicion for multiple sclerosis (MS). However, occlusive retinopathy, hearing loss and absence of CSF oligoclonal bands are atypical for MS and should make the clinician consider an alternative diagnosis. We describe a man with hearing loss, visual signs and symptoms, and an accumulating burden of brain lesions, who was treated for a clinical diagnosis of MS for nearly two decades. Genetic testing revealed a unifying diagnosis.


Asunto(s)
Pérdida Auditiva Unilateral/etiología , Enfermedad de la Hemoglobina SC/diagnóstico , Hemoglobinas Anormales/genética , Leucoencefalopatías/etiología , Esclerosis Múltiple/diagnóstico , Trastornos de la Visión/etiología , Secuenciación del Exoma Completo , Errores Diagnósticos , Predisposición Genética a la Enfermedad , Pérdida Auditiva Unilateral/diagnóstico , Pérdida Auditiva Unilateral/fisiopatología , Enfermedad de la Hemoglobina SC/complicaciones , Enfermedad de la Hemoglobina SC/genética , Humanos , Leucoencefalopatías/diagnóstico por imagen , Leucoencefalopatías/fisiopatología , Imagen por Resonancia Magnética , Masculino , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/tratamiento farmacológico , Fenotipo , Valor Predictivo de las Pruebas , Trastornos de la Visión/diagnóstico , Trastornos de la Visión/fisiopatología , Adulto Joven
15.
Curr Opin Psychiatry ; 34(2): 177-185, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33395100

RESUMEN

PURPOSE OF REVIEW: Over 70 million people worldwide, including those with neurodegenerative disease (NDD), have been diagnosed with coronavirus disease 2019 (COVID-19) to date. We review outcomes in patients with NDD and COVID-19 and discuss the hypothesis that due to putative commonalities of neuropathogenesis, COVID-19 may unmask or trigger NDD in vulnerable individuals. RECENT FINDINGS: Based on a systematic review of published literature, patients with NDD, including dementia, Parkinson's disease, and multiple sclerosis (MS) make up a significant portion of hospitalized COVID-19 patients. Such patients are likely to present with altered mental status or worsening of their preexisting neurological symptoms. Patients with NDD and poor outcomes often have high-risk comorbid conditions, including advanced age, hypertension, diabetes, obesity, and heart/lung disease. Patients with dementia including Alzheimer's disease are at higher risk for hospitalization and death, whereas those with preexisting Parkinson's disease are not. MS patients have good outcomes and disease modifying therapies do not increase the risk for severe disease. Viral infections and attendant neuroinflammation have been associated with the pathogenesis of Alzheimer's disease, Parkinson's disease, and MS, suggesting that COVID-19 may have the potential to incite or accelerate neurodegeneration. SUMMARY: Since patients with Alzheimer's disease are at higher risk for hospitalization and death in the setting of COVID-19, additional precautions and protective measures should be put in place to prevent infections and optimize management of comorbidities in this vulnerable population. Further studies are needed to determine whether COVID-19 may lead to an increased risk of developing NDD in susceptible individuals.


Asunto(s)
/complicaciones , Demencia/complicaciones , Hospitalización , Esclerosis Múltiple/complicaciones , Enfermedad de Parkinson/complicaciones , Humanos , Pronóstico , Factores de Riesgo
16.
Ann Neurol ; 89(4): 780-789, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33480077

RESUMEN

OBJECTIVE: This study was undertaken to assess the impact of immunosuppressive and immunomodulatory therapies on the severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (PwMS). METHODS: We retrospectively collected data of PwMS with suspected or confirmed COVID-19. All the patients had complete follow-up to death or recovery. Severe COVID-19 was defined by a 3-level variable: mild disease not requiring hospitalization versus pneumonia or hospitalization versus intensive care unit (ICU) admission or death. We evaluated baseline characteristics and MS therapies associated with severe COVID-19 by multivariate and propensity score (PS)-weighted ordinal logistic models. Sensitivity analyses were run to confirm the results. RESULTS: Of 844 PwMS with suspected (n = 565) or confirmed (n = 279) COVID-19, 13 (1.54%) died; 11 of them were in a progressive MS phase, and 8 were without any therapy. Thirty-eight (4.5%) were admitted to an ICU; 99 (11.7%) had radiologically documented pneumonia; 96 (11.4%) were hospitalized. After adjusting for region, age, sex, progressive MS course, Expanded Disability Status Scale, disease duration, body mass index, comorbidities, and recent methylprednisolone use, therapy with an anti-CD20 agent (ocrelizumab or rituximab) was significantly associated (odds ratio [OR] = 2.37, 95% confidence interval [CI] = 1.18-4.74, p = 0.015) with increased risk of severe COVID-19. Recent use (<1 month) of methylprednisolone was also associated with a worse outcome (OR = 5.24, 95% CI = 2.20-12.53, p = 0.001). Results were confirmed by the PS-weighted analysis and by all the sensitivity analyses. INTERPRETATION: This study showed an acceptable level of safety of therapies with a broad array of mechanisms of action. However, some specific elements of risk emerged. These will need to be considered while the COVID-19 pandemic persists. ANN NEUROL 2021;89:780-789.


Asunto(s)
/fisiopatología , Hospitalización/estadística & datos numéricos , Inmunosupresores/uso terapéutico , Esclerosis Múltiple/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales Humanizados/uso terapéutico , /mortalidad , Dimetilfumarato/uso terapéutico , Femenino , Clorhidrato de Fingolimod/uso terapéutico , Humanos , Factores Inmunológicos/uso terapéutico , Unidades de Cuidados Intensivos/estadística & datos numéricos , Interferones/uso terapéutico , Masculino , Persona de Mediana Edad , Mortalidad , Esclerosis Múltiple/complicaciones , Natalizumab/uso terapéutico , Índice de Severidad de la Enfermedad , Adulto Joven
17.
Nervenarzt ; 92(4): 349-358, 2021 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-33399923

RESUMEN

BACKGROUND: In the clinical management of patients with multiple sclerosis (MS), the challenge is to make an early diagnosis and initiate adequate treatment of neurogenic disorders of the lower urinary tract (NLUTD). Various national guidelines provide practical recommendations which are sometimes discordant. OBJECTIVE: To develop a simple evidence-based algorithm for detecting NLUTD in patients with MS that could be taken as a principle for deriving therapeutic consequences. MATERIAL AND METHODS: A prospective multicenter study was initiated as a direct result of two multidisciplinary conferences. The aim was to identify statistically and clinically relevant parameters for the routine diagnosis of NLUTD in patients with MS. Urodynamic abnormalities served as the gold standard. At three subsequent consensus conferences, the results of the study were discussed, a diagnostic algorithm was developed and consensus was reached on a first-line treatment. RESULTS AND DISCUSSION: The proposed algorithm enables the detection of NLUTD in patients with MS with the help of four statistically significant predictors: 1) the residual urine volume, 2) the number of urinary tract infections (UTI) within the last 6 months, 3) the standardized micturition frequency and 4) the presence/absence of urinary incontinence. The newly developed algorithm has proved to be efficient with the following results: approximately 75% of the patients do not need a urodynamic examination for a first-line treatment decision. In 25% of cases, urodynamic examinations are essential for an adequate treatment decision. Routine assessments include the patient medical history, residual urine volume measurement, a micturition diary and a uroflowmetry (optional).


Asunto(s)
Esclerosis Múltiple , Enfermedades Urológicas , Humanos , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/diagnóstico , Estudios Prospectivos , Urodinámica
18.
Mult Scler Relat Disord ; 49: 102725, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33482590

RESUMEN

BACKGROUND: There are limited data on the impact of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on people with multiple sclerosis (MS). OBJECTIVE: To better understand SARS-CoV-2 infection in ocrelizumab-treated people with MS. METHODS: Internal Roche/Genentech data sources: Cases of COVID-19 from ongoing Roche/Genentech clinical trials and from post-marketing use of ocrelizumab until July 31, 2020 were identified and assessed using descriptive statistics. External real-world data (RWD) source: An MS COVID-19 cohort and an ocrelizumab-treated MS COVID-19 cohort were identified and assessed from the OPTUMⓇ de-identified COVID-19 electronic health record (EHR) database. RESULTS: Roche/Genentech clinical trial data: There were 51 (1.3%) suspected or confirmed cases of COVID-19 identified from 4,000 patients ongoing in 10 Roche/Genentech clinical trials. Of these, 26 (51%) were confirmed COVID-19 and 25 (49%) were suspected COVID-19. Sixteen (31.4%) patients were hospitalized. COVID-19 severity was mild to moderate in most patients (35, 68.6%). Ten (19.6%) patients had severe disease and there were three (5.9%) fatal cases. Most patients (43, 84.3%) recovered or were recovering. There was no association apparent between duration of exposure to ocrelizumab and COVID-19. Among COVID-19 patients with previous serum immunoglobulin status (27/51, 52.9%), all (27/27, 100%) had IgG levels within the normal range. Roche/Genentech post-marketing safety database data: There were 307 post-marketing cases of COVID-19 in the Roche/Genentech global safety database. Of these, 263 (85.7%) were confirmed and 44 (14.3%) were suspected COVID-19. 100 (32.6%) patients were hospitalized. COVID-19 was asymptomatic, mild or moderate in 143 (46.6%) patients, severe in 52 (16.9%) patients, and critical in 15 (4.9%) patients. There were 17 (5.5%) fatal cases. Information on severity was not reported in 80 (26.1%) cases. Most patients (211, 68.7%) recovered or were recovering at the time of the report. External RWD data source: As of July 13, 2020, the OPTUMⓇ database included EHRs for almost 1.2 million patients with suspected COVID-19, 130,500 of whom met the criteria for confirmed/clinically diagnosed COVID-19. A total of 357 patients with MS with confirmed COVID-19 were identified. Forty-eight (13.4%) were treated with ocrelizumab, of whom 12 (25.0%) were hospitalized and one died (2.1%). Similar rates of hospitalization, invasive ventilation, and death were observed in the ocrelizumab-treated and non-ocrelizumab-treated MS cohorts. Across the Roche/Genentech and RWD sources assessed, age, male sex, and the presence of comorbidities such as hypertension were associated with a more severe disease course of COVID-19. There was a higher number of comorbidities present in hospitalized versus non-hospitalized patients. CONCLUSIONS: This assessment provides evidence that COVID-19 in ocrelizumab-treated people with MS is predominantly mild to moderate in severity with most patients not requiring hospitalization; in line with data reported from the general population and MS datasets. Risk factors known to be associated with severe COVID-19 outcomes in the general population also appear to influence COVID-19 severity in ocrelizumab-treated people with MS. Case fatality rates for ocrelizumab-treated people with MS were within published ranges for the general population and other MS cohorts.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Esclerosis Múltiple , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Registros Electrónicos de Salud , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/complicaciones , Esclerosis Múltiple/tratamiento farmacológico , Factores de Riesgo , Adulto Joven
19.
Nat Commun ; 12(1): 105, 2021 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-33397973

RESUMEN

Environmental triggers have important functions in multiple sclerosis (MS) susceptibility, phenotype, and trajectory. Exposure to early life trauma (ELT) has been associated with higher relapse rates in MS patients; however, the underlying mechanisms are not well-defined. Here we show ELT induces mechanistic and phenotypical alterations during experimental autoimmune encephalitis (EAE). ELT sustains downregulation of immune cell adrenergic receptors, which can be attributed to chronic norepinephrine circulation. ELT-subjected mice exhibit interferon-ß resistance and neurodegeneration driven by lymphotoxin and CXCR2 involvement. These phenotypic changes are observed in control EAE mice treated with ß1 adrenergic receptor antagonist. Conversely, ß1 adrenergic receptor agonist treatment to ELT mice abrogates phenotype changes via restoration of immune cell ß1 adrenergic receptor function. Our results indicate that ELT alters EAE phenotype via downregulation of ß1 adrenergic signaling in immune cells. These results have implications for the effect of environmental factors in provoking disease heterogeneity and might enable prediction of long-term outcomes in MS.


Asunto(s)
Regulación hacia Abajo , Interferón beta/metabolismo , Esclerosis Múltiple/complicaciones , Degeneración Nerviosa/complicaciones , Receptores Adrenérgicos beta 1/metabolismo , Transducción de Señal , Estrés Psicológico/complicaciones , Agonistas de Receptores Adrenérgicos beta 1/farmacología , Antagonistas de Receptores Adrenérgicos beta 1/farmacología , Animales , Biomarcadores/metabolismo , Encéfalo/inmunología , Encéfalo/patología , Células Dendríticas/efectos de los fármacos , Células Dendríticas/metabolismo , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/sangre , Encefalomielitis Autoinmune Experimental/patología , Femenino , Aparato de Golgi/metabolismo , Masculino , Ratones Endogámicos C57BL , Esclerosis Múltiple/sangre , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/patología , Degeneración Nerviosa/sangre , Degeneración Nerviosa/inmunología , Degeneración Nerviosa/patología , Neuronas/metabolismo , Neuronas/patología , Norepinefrina/sangre , Fenotipo , Índice de Severidad de la Enfermedad , Regulación hacia Arriba/efectos de los fármacos
20.
Braz J Med Biol Res ; 54(3): e10428, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33470393

RESUMEN

There is increasing evidence that neurofilament light chain (NF-L) can be considered as a biomarker for neuro-axonal damage. This polypeptide can be released into the cerebrospinal fluid (CSF) and the blood, where it can be quantified. The concentration of NF-L is elevated in patients with multiple sclerosis (MS) and psychiatric disorders. We aimed to investigate the NF-L levels in the CSF from treated MS patients and the relationship with depression or anxiety. The study involved three groups: control group (individuals without inflammation), the relapse-remitting multiple sclerosis (RRMS)-untreated group, and the RRMS-Fingo group (RRMS patients who were treated with fingolimod). MS disability was assessed by the Expanded Disability Status Scale, and depression and anxiety were evaluated by a neuropsychologist, using the Hospital Anxiety and Depression Scale, the Beck Depression Inventory-II, and the Beck Anxiety Inventory. Individual CSF samples were collected to measure NF-L levels. The results of the statistical analysis on levels of NF-L in the CSF of control subjects, RRMS-untreated patients, and RRMS-Fingo patients were significant. The relationship between depression and anxiety in RRMS-Fingo patients and NF-L levels was not statistically significant. In conclusion, MS events such as anxiety and depression appear to contribute to the onset of clinical relapses, subclinical cases, and neurodegeneration.


Asunto(s)
Trastornos de Ansiedad , Depresión , Esclerosis Múltiple , Trastornos de Ansiedad/etiología , Biomarcadores , Depresión/etiología , Humanos , Filamentos Intermedios , Esclerosis Múltiple/complicaciones , Proteínas de Neurofilamentos
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