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1.
Cell ; 186(7): 1309-1327, 2023 03 30.
Artículo en Inglés | MEDLINE | ID: mdl-37001498

RESUMEN

Multiple sclerosis (MS) is a chronic inflammatory and degenerative disease of the central nervous system afflicting nearly three million individuals worldwide. Neuroimmune interactions between glial, neural, and immune cells play important roles in MS pathology and offer potential targets for therapeutic intervention. Here, we review underlying risk factors, mechanisms of MS pathogenesis, available disease modifying therapies, and examine the value of emerging technologies, which may address unmet clinical needs and identify novel therapeutic targets.


Asunto(s)
Esclerosis Múltiple , Humanos , Esclerosis Múltiple/tratamiento farmacológico , Sistema Nervioso Central , Neuroglía , Fenómenos Fisiológicos Celulares , Inflamación/patología
2.
Nat Immunol ; 20(1): 109, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30448856

RESUMEN

In the version of this article initially published, in the legend to Fig. 1b, the description of the frequency of TH17-IL-10+ clones was incomplete for the first group; this should read as follows: "...13 experiments with clones isolated from CCR6+CCR4+CXCR3- T cells...". Also, the label along the vertical axis of the bottom right plot in Figure 5b was incomplete; the correct label is 'IFN-γ+ cells (%)'. Finally, in the first sentence of the final paragraph of the final Results subsection, the description of the regions analyzed was incorrect; that sentence should begin: "DNA motif-enrichment analysis of the subset-specific H3K27ac-positive regions...". The errors have been corrected in the HTML and PDF versions of the article.

3.
Immunity ; 55(3): 390-392, 2022 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-35263566

RESUMEN

Epstein-Barr virus (EBV) is a putative trigger for multiple sclerosis (MS), but clear causality is lacking. In a recent issue of Science, Bjornevik and Cortese et al. utilize longitudinal evaluation of over 10 million adults to demonstrate increased MS risk after EBV infection.


Asunto(s)
Infecciones por Virus de Epstein-Barr , Esclerosis Múltiple , Adulto , Herpesvirus Humano 4 , Humanos , Esclerosis Múltiple/etiología
4.
Nat Immunol ; 19(10): 1126-1136, 2018 10.
Artículo en Inglés | MEDLINE | ID: mdl-30201991

RESUMEN

Different types of effector and memory T lymphocytes are induced and maintained in protective or pathological immune responses. Here we characterized two human CD4+ TH17 helper cell subsets that, in the recently activated state, could be distinguished on the basis of their expression of the anti-inflammatory cytokine IL-10. IL-10+ TH17 cells upregulated a variety of genes encoding immunoregulatory molecules, as well as genes whose expression is characteristic of tissue-resident T cells. In contrast, IL-10- TH17 cells maintained a pro-inflammatory gene-expression profile and upregulated the expression of homing receptors that guide recirculation from tissues to blood. Expression of the transcription factor c-MAF was selectively upregulated in IL-10+ TH17 cells, and it was bound to a large set of enhancer-like regions and modulated the immunoregulatory and tissue-residency program. Our results identify c-MAF as a relevant factor that drives two highly divergent post-activation fates of human TH17 cells and provide a framework with which to investigate the role of these cells in physiology and immunopathology.


Asunto(s)
Interleucina-10/inmunología , Proteínas Proto-Oncogénicas c-maf/inmunología , Subgrupos de Linfocitos T/inmunología , Células Th17/inmunología , Quimiotaxis de Leucocito/inmunología , Regulación de la Expresión Génica/inmunología , Humanos , Inflamación/inmunología , Interleucina-10/biosíntesis , Proteínas Proto-Oncogénicas c-maf/metabolismo , Subgrupos de Linfocitos T/metabolismo , Células Th17/metabolismo
5.
Immunity ; 53(4): 707-709, 2020 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-33053328

RESUMEN

The microbiome plays an important role in multiple sclerosis. In a recent issue of Nature, Miyauchi et al. report that gut microbial molecular mimicry in concert with gut microbes that enhance Th17 cells act synergistically to worsen CNS autoimmunity.


Asunto(s)
Microbioma Gastrointestinal , Esclerosis Múltiple , Autoinmunidad , Humanos , Inflamación , Médula Espinal
6.
Immunity ; 47(3): 566-581.e9, 2017 09 19.
Artículo en Inglés | MEDLINE | ID: mdl-28930663

RESUMEN

Microglia play a pivotal role in the maintenance of brain homeostasis but lose homeostatic function during neurodegenerative disorders. We identified a specific apolipoprotein E (APOE)-dependent molecular signature in microglia from models of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Alzheimer's disease (AD) and in microglia surrounding neuritic ß-amyloid (Aß)-plaques in the brains of people with AD. The APOE pathway mediated a switch from a homeostatic to a neurodegenerative microglia phenotype after phagocytosis of apoptotic neurons. TREM2 (triggering receptor expressed on myeloid cells 2) induced APOE signaling, and targeting the TREM2-APOE pathway restored the homeostatic signature of microglia in ALS and AD mouse models and prevented neuronal loss in an acute model of neurodegeneration. APOE-mediated neurodegenerative microglia had lost their tolerogenic function. Our work identifies the TREM2-APOE pathway as a major regulator of microglial functional phenotype in neurodegenerative diseases and serves as a novel target that could aid in the restoration of homeostatic microglia.


Asunto(s)
Apolipoproteínas E/metabolismo , Glicoproteínas de Membrana/metabolismo , Microglía/metabolismo , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/metabolismo , Receptores Inmunológicos/metabolismo , Transducción de Señal , Transcriptoma , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Apolipoproteínas E/deficiencia , Apolipoproteínas E/genética , Apoptosis/genética , Apoptosis/inmunología , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Análisis por Conglomerados , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Marcación de Gen , Humanos , Tolerancia Inmunológica , Ratones , Ratones Noqueados , Ratones Transgénicos , Microglía/inmunología , Monocitos/inmunología , Monocitos/metabolismo , Enfermedades Neurodegenerativas/inmunología , Neuronas/metabolismo , Fagocitosis/genética , Fagocitosis/inmunología , Fenotipo , Placa Amiloide/metabolismo , Placa Amiloide/patología , Superóxido Dismutasa-1/genética , Superóxido Dismutasa-1/metabolismo , Factor de Crecimiento Transformador beta/metabolismo
7.
Proc Natl Acad Sci U S A ; 120(11): e2220272120, 2023 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-36881624

RESUMEN

T cells are present in early stages of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and play a major role in disease outcome and long-lasting immunity. Nasal administration of a fully human anti-CD3 monoclonal antibody (Foralumab) reduced lung inflammation as well as serum IL-6 and C-reactive protein in moderate cases of COVID-19. Using serum proteomics and RNA-sequencing, we investigated the immune changes in patients treated with nasal Foralumab. In a randomized trial, mild to moderate COVID-19 outpatients received nasal Foralumab (100 µg/d) given for 10 consecutive days and were compared to patients that did not receive Foralumab. We found that naïve-like T cells were increased in Foralumab-treated subjects and NGK7+ effector T cells were reduced. CCL5, IL32, CST7, GZMH, GZMB, GZMA, PRF1, and CCL4 gene expression were downregulated in T cells and CASP1 was downregulated in T cells, monocytes, and B cells in subjects treated with Foralumab. In addition to the downregulation of effector features, an increase in TGFB1 gene expression in cell types with known effector function was observed in Foralumab-treated subjects. We also found increased expression of GTP-binding gene GIMAP7 in subjects treated with Foralumab. Rho/ROCK1, a downstream pathway of GTPases signaling was downregulated in Foralumab-treated individuals. TGFB1, GIMAP7, and NKG7 transcriptomic changes observed in Foralumab-treated COVID-19 subjects were also observed in healthy volunteers, MS subjects, and mice treated with nasal anti-CD3. Our findings demonstrate that nasal Foralumab modulates the inflammatory response in COVID-19 and provides a novel avenue to treat the disease.


Asunto(s)
Anticuerpos Monoclonales , COVID-19 , Animales , Humanos , Ratones , Administración Intranasal , Anticuerpos Monoclonales/uso terapéutico , Proteínas de Unión al GTP , Proteínas de la Membrana , Quinasas Asociadas a rho , SARS-CoV-2 , Linfocitos T , Factor de Crecimiento Transformador beta1/genética
8.
Proc Natl Acad Sci U S A ; 120(37): e2309221120, 2023 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-37669383

RESUMEN

Emerging evidence suggests that dysregulation of neuroinflammation, particularly that orchestrated by microglia, plays a significant role in the pathogenesis of Alzheimer's disease (AD). Danger signals including dead neurons, dystrophic axons, phosphorylated tau, and amyloid plaques alter the functional phenotype of microglia from a homeostatic (M0) to a neurodegenerative or disease-associated phenotype, which in turn drives neuroinflammation and promotes disease. Thus, therapies that target microglia activation constitute a unique approach for treating AD. Here, we report that nasally administered anti-CD3 monoclonal antibody in the 3xTg AD mouse model reduced microglial activation and improved cognition independent of amyloid beta deposition. In addition, gene expression analysis demonstrated decreased oxidative stress, increased axogenesis and synaptic organization, and metabolic changes in the hippocampus and cortex of nasal anti-CD3 treated animals. The beneficial effect of nasal anti-CD3 was associated with the accumulation of T cells in the brain where they were in close contact with microglial cells. Taken together, our findings identify nasal anti-CD3 as a unique form of immunotherapy to treat Alzheimer's disease independent of amyloid beta targeting.


Asunto(s)
Enfermedad de Alzheimer , Animales , Ratones , Administración Intranasal , Péptidos beta-Amiloides , Enfermedades Neuroinflamatorias , Anticuerpos Monoclonales , Modelos Animales de Enfermedad
9.
Brain Behav Immun ; 117: 242-254, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38281671

RESUMEN

Intestinal γδ T cells play an important role in shaping the gut microbiota, which is critical not only for maintaining intestinal homeostasis but also for controlling brain function and behavior. Here, we found that mice deficient for γδ T cells (γδ-/-) developed an abnormal pattern of repetitive/compulsive (R/C) behavior, which was dependent on the gut microbiota. Colonization of WT mice with γδ-/- microbiota induced R/C behavior whereas colonization of γδ-/- mice with WT microbiota abolished the R/C behavior. Moreover, γδ-/- mice had elevated levels of the microbial metabolite 3-phenylpropanoic acid in their cecum, which is a precursor to hippurate (HIP), a metabolite we found to be elevated in the CSF. HIP reaches the striatum and activates dopamine type 1 (D1R)-expressing neurons, leading to R/C behavior. Altogether, these data suggest that intestinal γδ T cells shape the gut microbiota and their metabolites and prevent dysfunctions of the striatum associated with behavior modulation.


Asunto(s)
Microbioma Gastrointestinal , Hipuratos , Linfocitos T , Animales , Ratones , Cuerpo Estriado , Neuronas , Conducta Compulsiva
10.
Epilepsia ; 65(8): 2423-2437, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38943543

RESUMEN

OBJECTIVES: A surgical "treatment gap" in pediatric epilepsy persists despite the demonstrated safety and effectiveness of surgery. For this reason, the national surgical landscape should be investigated such that an updated assessment may more appropriately guide health care efforts. METHODS: In our retrospective cross-sectional observational study, the National Inpatient Sample (NIS) database was queried for individuals 0 to <18 years of age who had an International Classification of Diseases (ICD) code for drug-resistant epilepsy (DRE). This cohort was then split into a medical group and a surgical group. The former was defined by ICD codes for -DRE without an accompanying surgical code, and the latter was defined by DRE and one of the following epilepsy surgeries: any open surgery; laser interstitial thermal therapy (LITT); vagus nerve stimulation; or responsive neurostimulation (RNS) from 1998 to 2020. Demographic variables of age, gender, race, insurance type, hospital charge, and hospital characteristics were analyzed between surgical options. Continuous variables were analyzed with weight-adjusted quantile regression analysis, and categorical variables were analyzed by weight-adjusted counts with percentages and compared with weight-adjusted chi-square test results. RESULTS: These data indicate an increase in epilepsy surgeries over a 22-year period, primarily due to a statistically significant increase in open surgery and a non-significant increase in minimally invasive techniques, such as LITT and RNS. There are significant differences in age, race, gender, insurance type, median household income, Elixhauser index, hospital setting, and size between the medical and surgical groups, as well as the procedure performed. SIGNIFICANCE: An increase in open surgery and minimally invasive surgeries (LITT and RNS) account for the overall rise in pediatric epilepsy surgery over the last 22 years. A positive inflection point in open surgery is seen in 2005. Socioeconomic disparities exist between medical and surgical groups. Patient and hospital sociodemographics show significant differences between the procedure performed. Further efforts are required to close the surgical "treatment gap."


Asunto(s)
Epilepsia Refractaria , Procedimientos Quirúrgicos Mínimamente Invasivos , Humanos , Masculino , Femenino , Niño , Adolescente , Preescolar , Lactante , Estudios Retrospectivos , Estudios Transversales , Procedimientos Quirúrgicos Mínimamente Invasivos/estadística & datos numéricos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Epilepsia Refractaria/cirugía , Recién Nacido , Estimulación del Nervio Vago , Estados Unidos , Procedimientos Neuroquirúrgicos/tendencias , Procedimientos Neuroquirúrgicos/estadística & datos numéricos , Procedimientos Neuroquirúrgicos/métodos , Epilepsia/cirugía
11.
Epilepsia ; 65(1): 46-56, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37347512

RESUMEN

OBJECTIVES: Although hemispheric surgeries are among the most effective procedures for drug-resistant epilepsy (DRE) in the pediatric population, there is a large variability in seizure outcomes at the group level. A recently developed HOPS score provides individualized estimation of likelihood of seizure freedom to complement clinical judgement. The objective of this study was to develop a freely accessible online calculator that accurately predicts the probability of seizure freedom for any patient at 1-, 2-, and 5-years post-hemispherectomy. METHODS: Retrospective data of all pediatric patients with DRE and seizure outcome data from the original Hemispherectomy Outcome Prediction Scale (HOPS) study were included. The primary outcome of interest was time-to-seizure recurrence. A multivariate Cox proportional-hazards regression model was developed to predict the likelihood of post-hemispheric surgery seizure freedom at three time points (1-, 2- and 5- years) based on a combination of variables identified by clinical judgment and inferential statistics predictive of the primary outcome. The final model from this study was encoded in a publicly accessible online calculator on the International Network for Epilepsy Surgery and Treatment (iNEST) website (https://hops-calculator.com/). RESULTS: The selected variables for inclusion in the final model included the five original HOPS variables (age at seizure onset, etiologic substrate, seizure semiology, prior non-hemispheric resective surgery, and contralateral fluorodeoxyglucose-positron emission tomography [FDG-PET] hypometabolism) and three additional variables (age at surgery, history of infantile spasms, and magnetic resonance imaging [MRI] lesion). Predictors of shorter time-to-seizure recurrence included younger age at seizure onset, prior resective surgery, generalized seizure semiology, FDG-PET hypometabolism contralateral to the side of surgery, contralateral MRI lesion, non-lesional MRI, non-stroke etiologies, and a history of infantile spasms. The area under the curve (AUC) of the final model was 73.0%. SIGNIFICANCE: Online calculators are useful, cost-free tools that can assist physicians in risk estimation and inform joint decision-making processes with patients and families, potentially leading to greater satisfaction. Although the HOPS data was validated in the original analysis, the authors encourage external validation of this new calculator.


Asunto(s)
Epilepsia Refractaria , Epilepsia , Hemisferectomía , Espasmos Infantiles , Niño , Humanos , Hemisferectomía/métodos , Espasmos Infantiles/cirugía , Estudios Retrospectivos , Fluorodesoxiglucosa F18 , Resultado del Tratamiento , Epilepsia/diagnóstico por imagen , Epilepsia/cirugía , Convulsiones/diagnóstico , Convulsiones/etiología , Convulsiones/cirugía , Epilepsia Refractaria/diagnóstico por imagen , Epilepsia Refractaria/cirugía , Imagen por Resonancia Magnética , Electroencefalografía
12.
Adv Tech Stand Neurosurg ; 49: 291-306, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38700689

RESUMEN

Pediatric epilepsy has a worldwide prevalence of approximately 1% (Berg et al., Handb Clin Neurol 111:391-398, 2013) and is associated with not only lower quality of life but also long-term deficits in executive function, significant psychosocial stressors, poor cognitive outcomes, and developmental delays (Schraegle and Titus, Epilepsy Behav 62:20-26, 2016; Puka and Smith, Epilepsia 56:873-881, 2015). With approximately one-third of patients resistant to medical control, surgical intervention can offer a cure or palliation to decrease the disease burden and improve neurological development. Despite its potential, epilepsy surgery is drastically underutilized. Even today only 1% of the millions of epilepsy patients are referred annually for neurosurgical evaluation, and the average delay between diagnosis of Drug Resistant Epilepsy (DRE) and surgical intervention is approximately 20 years in adults and 5 years in children (Solli et al., Epilepsia 61:1352-1364, 2020). It is still estimated that only one-third of surgical candidates undergo operative intervention (Pestana Knight et al., Epilepsia 56:375, 2015). In contrast to the stable to declining rates of adult epilepsy surgery (Englot et al., Neurology 78:1200-1206, 2012; Neligan et al., Epilepsia 54:e62-e65, 2013), rates of pediatric surgery are rising (Pestana Knight et al., Epilepsia 56:375, 2015). Innovations in surgical approaches to epilepsy not only minimize potential complications but also expand the definition of a surgical candidate. In this chapter, three alternatives to classical resection are presented. First, laser ablation provides a minimally invasive approach to focal lesions. Next, both central and peripheral nervous system stimulation can interrupt seizure networks without creating permanent lesions. Lastly, focused ultrasound is discussed as a potential new avenue not only for ablation but also modulation of small, deep foci within seizure networks. A better understanding of the potential surgical options can guide patients and providers to explore all treatment avenues.


Asunto(s)
Epilepsia , Procedimientos Neuroquirúrgicos , Niño , Humanos , Epilepsia Refractaria/cirugía , Epilepsia Refractaria/diagnóstico por imagen , Epilepsia/cirugía , Terapia por Láser/métodos , Procedimientos Neuroquirúrgicos/métodos
13.
Childs Nerv Syst ; 40(8): 2367-2372, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38856743

RESUMEN

INTRODUCTION: Outcomes for pineal region and superior cerebellar tumors in young children often hinge on extent of microsurgical resection, and thus choosing an approach that provides adequate visualization of pathology is essential. The occipital interhemispheric transtentorial (OITT) approach provides excellent exposure while minimizing cerebellar retraction. However, this approach has not been widely accepted as a viable option for very young children due to concerns for potential blood loss when incising the tentorium. The aim of this paper is to characterize our recent institutional experience with the occipital interhemispheric transtentorial approach (OITT) for tumor resection in infants and toddlers. METHODS: A retrospective study was performed between 2016 and 2023 of pediatric patients less than 36 months of age who underwent OITT for tumor resection at a high-volume referral center. Patients with at least 3 months of postoperative follow-up and postoperative MRI were included. Primary outcomes included extent of resection, intraoperative and postoperative complications, and neurologic outcome. Secondary outcomes included length of stay and estimated blood loss. RESULTS: Eight patients, five male, were included. The median age at the time of surgery was 10 months (range 5-36 months). Presenting symptoms included macrocephaly, nausea/vomiting, strabismus, gait instability, or milestone regression. Hydrocephalus was present preoperatively in all patients. Average tumor volume was 38.6 cm3, ranging from 1.3 to 71.9 cm3. All patients underwent an OITT approach for tumor resection with stereotactic guidance. No intraoperative complications occurred, and no permanent neurologic deficits developed postoperatively. Gross total resection was achieved in all cases per postoperative MRI report, and no instances of new cerebellar, brainstem, or occipital lobe ischemia were noted. CONCLUSIONS: OITT approach for tumor resection in very young children (≤ 36 months) is an effective strategy with an acceptable safety profile. In our series, no significant intraoperative or postoperative complications occurred. To our knowledge, this is the first report describing this technique specifically in patients less than 36 months of age.


Asunto(s)
Procedimientos Neuroquirúrgicos , Complicaciones Posoperatorias , Humanos , Lactante , Masculino , Femenino , Estudios Retrospectivos , Preescolar , Procedimientos Neuroquirúrgicos/métodos , Complicaciones Posoperatorias/etiología , Resultado del Tratamiento , Neoplasias Cerebelosas/cirugía , Neoplasias Encefálicas/cirugía , Pinealoma/cirugía
14.
Childs Nerv Syst ; 40(4): 1239-1244, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38032484

RESUMEN

PURPOSE: Epilepsy surgery for pediatric drug-resistant epilepsy has been shown to improve seizure control, enhance patient and family QoL, and reduce mortality. However, diagnostic tools and surgical capacity are less accessible worldwide. The International Society Pediatric Neurosurgery (ISPN) has established a Pediatric Epilepsy Surgery Interest Group (PESIG), aiming to enhance global collaboration in research and educational aspects. The goals of this manuscript are to introduce PESIG and analyze geographical differences of epilepsy surgery and technology availability. METHODS: PESIG was established (2022) following an ISPN executive board decision. Using a standardized form, we surveyed the PESIG members, collecting and analyzing data regarding geographical distribution, and availability of various epilepsy treatment-related technologies. RESULTS: Two hundred eighty-two members registered in PESIG from 70 countries, over 6 continents, were included. We categorized the countries by GDP as follows: low, lower-medium, upper-medium, and high income. The most commonly available technology was vagus nerve stimulation 68%. Stereoelectroencephalography was available for 58%. North America had statistically significant greater availability compared to other continents. Europe had greater availability compared to Africa, Asia, and South (Latin) America. Asia had greater availability compared to Africa. High-income countries had statistically significant greater availability compared to other income groups; there was no significant difference between the other income-level subgroups. CONCLUSION: There is a clear discrepancy between countries and continents regarding access to epilepsy surgery technologies. This strengthens the need for collaboration between neurologists and neurosurgeons from around the world, to enhance medical education and training, as well as to increase technological availability.


Asunto(s)
Epilepsia , Neurocirugia , Humanos , Niño , Neurocirugia/educación , Calidad de Vida , Opinión Pública , Procedimientos Neuroquirúrgicos , Epilepsia/cirugía
15.
Childs Nerv Syst ; 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39243333

RESUMEN

PURPOSE: Hemispherotomy is an effective surgery for intractable pediatric hemispheric epilepsy. Over the years, the surgical goal has shifted from a complete hemispheric resection (anatomical hemispherectomy) to a disconnective hemispherotomy (DH). Multiple techniques for DH have been described, and often, anterior temporal lobectomy (ATL, with hippocampal resection) is performed. The goal of the current study is to assess the role of hippocampal resection in DH. METHODS: We retrospectively collected all clinical data of children (< 18 years old) who underwent DH between 2001 and 2022 at two tertiary large centers. Epilepsy status and surgical outcome were compared, based on whether the hippocampus was resected (as part of an ATL) or disconnected at the amygdala and atrial segment of the fornix (with no ATL). RESULTS: A total of 86 patients (32 females) were included. The most common epilepsy etiologies were stroke (31), Rasmussen's encephalitis (16), cortical dysplasia (10), and hemimegaloencephaly (9). The mean age at surgery was 7 (± 4.9) years. The average number of anti-seizure medications (ASMs) at surgery was 3 (± 1.2). Hemispherotomy techniques included peri-insular (54), vertical (23 [19 endoscopic + 4 parasagittal]), and trans-sylvian (9). The mean follow-up was 41.5 (± 38) months. Forty-three patients had hippocampal resection, and 43 patients had a hippocampal disconnection. Both groups had similar Engel outcome scores (p = 0.53). CONCLUSIONS: Disconnective hemispherotomy is highly effective for pediatric intractable hemispheric epilepsy. Our data suggest that the inclusion of hippocampal resection does not provide additional benefit.

16.
J Craniofac Surg ; 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39186061

RESUMEN

Osteomas are benign bony lesions that can occur throughout the craniofacial skeleton. Surgical excision can be an effective treatment, as recurrence is relatively uncommon. Outside of incomplete resection, causes of recurrence are poorly documented, especially in the pediatric population. Exchange cranioplasty is an autologous reconstructive surgical option for patients of all ages, and it can be effective in the treatment of large calvarial osteomas. Recurrent lesions of the cranioplasty site have not been well described in the literature, with only 3 documented reports. In this study, we present a unique case of a recurrent osteoma at the site of a prior exchange cranioplasty. The authors also provide a systematic review of the literature for recurrent osteomas and highlight causes and conclusions for these lesions. Utilizing the PRISMA guidelines, a systematic review of articles published across databases was performed to identify accounts of recurrent osteomas at prior cranioplasty sites. Our systematic review illustrates that recurrent osteomas overlying different cranioplasty biomaterials is a rare entity and is due to incomplete resection of the galea and periosteum during the index procedure. Biomaterial selection for the pediatric population requires careful consideration before reconstruction. Though limited by 3 articles previously published and without a direct link to recurrence, long-term studies are needed to further guide biomaterial selection in the pediatric population to evaluate potential recurrences.

17.
Clin Immunol ; 253: 109688, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37414379

RESUMEN

An 18-protein multiple sclerosis (MS) disease activity (DA) test was validated based on associations between algorithm scores and clinical/radiographic assessments (N = 614 serum samples; Train [n = 426; algorithm development] and Test [n = 188; evaluation] subsets). The multi-protein model was trained based on presence/absence of gadolinium-positive (Gd+) lesions and was also strongly associated with new/enlarging T2 lesions, and active versus stable disease (composite of radiographic and clinical evidence of DA) with improved performance (p < 0.05) compared to the neurofilament light single protein model. The odds of having ≥1 Gd+ lesions with a moderate/high DA score were 4.49 times that of a low DA score, and the odds of having ≥2 Gd+ lesions with a high DA score were 20.99 times that of a low/moderate DA score. The MSDA Test was clinically validated with improved performance compared to the top-performing single-protein model and can serve as a quantitative tool to enhance the care of MS patients.


Asunto(s)
Esclerosis Múltiple , Humanos , Imagen por Resonancia Magnética , Proteínas Sanguíneas , Gadolinio , Algoritmos
18.
J Neuroinflammation ; 20(1): 136, 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-37264432

RESUMEN

BACKGROUND: Multiple sclerosis (MS) is a chronic demyelinating autoimmune disorder which may cause long-term disability. MicroRNA (miRNA) are stable, non-coding molecules that have been identified in our Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women's Hospital (CLIMB)-cohort, as well as other international cohorts, as potential disease biomarkers in MS. However, few studies have evaluated the association of miRNA expression early in the MS disease course with long-term outcomes. Therefore, we aimed to evaluate the potential role of three candidate serum miRNAs previously correlated with MS disability in patients with MS, miR-320b, miR-25-3p and miRNA 486-5p, as early biomarkers of MS disability at 10-year follow-up. MAIN BODY: We included 144 patients with serum obtained within three years of MS onset. miRNA expression was measured by RNA extraction followed by RT-PCR. Demographic, clinical, brain MRI and other biomarkers were collected. The primary outcome was the association between early miRNA expression and retaining benign MS, defined as EDSS ≤ 2 at 10-year follow-up. Among the 144 patients, 104 were benign and 40 were not benign at 10-year follow-up. 89 (62%) were women, with mean age at onset 37.7 (SD: 9.6) years. Patients who retained benign MS had lower values of miR-25-3p (p = 0.047) and higher miR-320b (p = 0.025) values. Development of SPMS was associated with higher miR-320b (p = 0.002) levels. Brain parenchymal fraction at year 10 was negatively correlated with miR-25-3p (p = 0.0004) and positively correlated with miR-320b (p = 0.006). No association was found between miR-486-5p and any outcome, and 10-year T2-lesion volume was not associated with any miRNA. CONCLUSIONS: Our results show that miR-320b and miR-25-3p expression are early biomarkers associated with MS severity and brain atrophy. This study provides class III evidence of that miR-320b and miR-25-3p are associated with long-term MS disability which may be a potential tool to risk-stratify patients with MS for early treatment decisions.


Asunto(s)
MicroARNs , Esclerosis Múltiple , Humanos , Femenino , Adulto , Masculino , MicroARNs/genética , Esclerosis Múltiple/genética , Estudios de Cohortes , Encéfalo , Biomarcadores
19.
J Neuroinflammation ; 20(1): 131, 2023 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-37254147

RESUMEN

BACKGROUND: Multiple sclerosis (MS) is a disabling autoimmune demyelinating disorder affecting young people and causing significant disability. In the last decade, different microRNA (miRNA) expression patterns have been associated to several treatment response therapies such as interferon and glatiramer acetate. Nowadays, there is increasing interest in the potential role of miRNA as treatment response biomarkers to the most recent oral and intravenous treatments. In this study, we aimed to evaluate serum miRNAs as biomarkers of No Evidence of Disease Activity (NEDA-3) at 2 years in patients with relapsing remitting MS (RRMS) treated with fingolimod. MAIN BODY: A Discovery cohort of 31 RRMS patients treated with fingolimod were identified from the CLIMB study and classified as No Evidence of Disease Activity (NEDA-3) or Evidence of Disease Activity (EDA-3) after 2 years on treatment. Levels of miRNA expression were measured at 6 months using human serum miRNA panels and compared in EDA-3 and NEDA-3 groups using the Wilcoxon rank sum test. A set of differentially expressed miRNA was further validated in an independent cohort of 22 fingolimod-treated patients. We found that 548a-3p serum levels were higher levels in fingolimod-treated patients classified as NEDA-3, compared to the EDA-3 group in both the Discovery (n = 31; p = 0.04) and Validation (n = 22; p = 0.03) cohorts 6 months after treatment initiation; miR-548a-3p provided an AUC of 0.882 discriminating patients with NEDA-3 at 2 years in the Validation cohort. CONCLUSION: Our results show differences in miR-548a-3p expression at 6 months after fingolimod start in patients with MS with NEDA-3 at 2 years. These results provide class III evidence of the use of miR-548a-3p as biomarker of NEDA-3 in patients with fingolimod.


Asunto(s)
Enfermedades Autoinmunes , MicroARNs , Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Humanos , Adolescente , Clorhidrato de Fingolimod/uso terapéutico , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico , Biomarcadores
20.
Ann Neurol ; 92(1): 87-96, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35429009

RESUMEN

OBJECTIVE: The objective of this study was to identify predictors in common between different clinical and magnetic resonance imaging (MRI) outcomes in multiple sclerosis (MS) by comparing predictive models. METHODS: We analyzed 704 patients from our center seen at MS onset, measuring 37 baseline demographic, clinical, treatment, and MRI predictors, and 10-year outcomes. Our primary aim was identifying predictors in common among clinical outcomes: aggressive MS, benign MS, and secondary-progressive (SP)MS. We also investigated MRI outcomes: T2 lesion volume (T2LV) and brain parenchymal fraction (BPF). The performance of the full 37-predictor model was compared with a least absolute shrinkage and selection operator (LASSO)-selected model of predictors in common between each outcome by the area under the receiver operating characteristic curves (AUCs). RESULTS: The full 37-predictor model was highly predictive of clinical outcomes: in-sample AUC was 0.91 for aggressive MS, 0.81 for benign MS, and 0.81 for SPMS. After variable selection, 10 LASSO-selected predictors were in common between each clinical outcome: age, Expanded Disability Status Scale, pyramidal, cerebellar, sensory and bowel/bladder signs, timed 25-foot walk ≥6 seconds, poor attack recovery, no sensory attacks, and time-to-treatment. This reduced model had comparable cross-validation AUC as the full 37-predictor model: 0.84 versus 0.81 for aggressive MS, 0.75 versus 0.73 for benign MS, and 0.76 versus 0.75 for SPMS, respectively. In contrast, 10-year MRI outcomes were more strongly influenced by initial T2LV and BPF than clinical outcomes. INTERPRETATION: Early prognostication of MS is possible using LASSO modeling to identify a limited set of accessible clinical features. These predictive models can be clinically usable in treatment decision making once implemented into web-based calculators. ANN NEUROL 2022;92:87-96.


Asunto(s)
Esclerosis Múltiple Crónica Progresiva , Esclerosis Múltiple , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Humanos , Imagen por Resonancia Magnética/métodos , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Esclerosis Múltiple Crónica Progresiva/diagnóstico
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