RESUMEN
The development of virtual care options, including virtual hospital platforms, is rapidly changing the healthcare, mostly in the pandemic period, due to difficulties in in-person consultations. For this purpose, in 2020, a neurological Virtual Hospital (NOVHO) pilot study has been implemented, in order to experiment a multidisciplinary second opinion evaluation system for neurological diseases. Cerebrovascular diseases represent a preponderant part of neurological disorders. However, more than 30% of strokes remain of undetermined source, and rare CVD (rCVD) are often misdiagnosed. The lack of data on phenotype and clinical course of rCVD patients makes the diagnosis and the development of therapies challenging. Since the diagnosis and care of rCVDs require adequate expertise and instrumental tools, their management is mostly allocated to a few experienced hospitals, making difficult equity in access to care. Therefore, strategies for virtual consultations are increasingly applied with some advantage for patient management also in peripheral areas. Moreover, health data are becoming increasingly complex and require new technologies to be managed. The use of Artificial Intelligence is beginning to be applied to the healthcare system and together with the Internet of Things will enable the creation of virtual models with predictive abilities, bringing healthcare one step closer to personalized medicine. Herein, we will report on the preliminary results of the NOVHO project and present the methodology of a new project aimed at developing an innovative multidisciplinary and multicentre virtual care model, specific for rCVD (NOVHO-rCVD), which combines the virtual hospital approach and the deep-learning machine system.
Asunto(s)
Inteligencia Artificial , Trastornos Cerebrovasculares , Humanos , Proyectos Piloto , Atención a la Salud , Trastornos Cerebrovasculares/diagnóstico , Trastornos Cerebrovasculares/terapia , HospitalesRESUMEN
Several neurological complications have been associated with the use of monoclonal antibodies (mAbs), and demyelinating disorders have been estimated to affect the 0.02-0.20% of treated patients. Alemtuzumab is a humanized chimeric mAbthat targets the CD52 antigen, it is currently approved for relapsed/refractory and high-risk untreated chronic lymphocytic leukemia (CLL). The major complication of alemtuzumab therapy is the increased risk of opportunistic infections secondary to the profound immunosuppression. Autoimmune diseases as Graves disease, immune thrombocytopenic purpura and Good pasture syndrome, have been reported to be associated to the treatment. In the present report, we present three CLL patients developing acute inflammatory demyelinating neuropathy during treatment with alemtuzumab. Despite the severity of the complication, all the patients showed an univocal good clinical response after treatment with intravenous immunoglobulin (IVIG). As alemtuzumab represents, nowadays, a key therapeutic option for CLL, clinicians should be aware of this rare and disabling toxicity.
Asunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Antineoplásicos/efectos adversos , Enfermedades Desmielinizantes , Inmunoglobulinas Intravenosas/administración & dosificación , Factores Inmunológicos/administración & dosificación , Enfermedades Renales , Enfermedad Aguda , Anciano , Alemtuzumab , Anticuerpos Monoclonales Humanizados/administración & dosificación , Antineoplásicos/administración & dosificación , Enfermedades Desmielinizantes/inducido químicamente , Enfermedades Desmielinizantes/tratamiento farmacológico , Humanos , Enfermedades Renales/inducido químicamente , Enfermedades Renales/tratamiento farmacológico , Masculino , Persona de Mediana EdadRESUMEN
Delirium is an acute confusional state characterized by altered level of consciousness and attention. Coronavirus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), can manifest itself with this neuropsychiatric disorder. The endpoints of our study were: the frequency of delirium in subjects with COVID-19 pneumonia; the risk factors that predispose to this condition; and the impact of delirium on mortality. Subjects were consecutively enrolled in a Geriatric Unit from January 5th to March 5th, 2021. Inclusion criteria were: diagnosis of SARS-CoV-2 infection, a radiologically documented pneumonia, and the ability of providing informed consent. Exclusion criteria were: absence of radiological evidence of pneumonia, sepsis, and the need of intensive care unit treatment. All subjects were evaluated by means of Richmond Agitation Sedation Scale (RASS) and Confusion Assessment Method-Intensive Care Unit (CAM-ICU) at least twice per day. In the study cohort (n = 71), twenty patients (28.2%) had delirium. Delirium was present on admission in 11.3%, and occurred during hospitalization in 19.0%. Compared to patients without delirium, patients who developed this neuropsychiatric disorder had a higher mortality rate (35% vs 5.9%) and an increased average hospital length of stay (21 days vs 17 days). In the multivariate analysis delirium was associated with frailty (OR = 2.81; CI = 1.4-5.8) and helmet ventilation (OR = 141.05; CI = 4.3-4663.9). Delirium was an independent predictor of mortality. Nearly a third of subjects (28.2%) had delirium during hospitalization for COVID-19. This finding supports the notion that delirium is a common complication of SARS-CoV2 infection. Since delirium is associated with longer hospital stay, and it is an independent marker of increased mortality, clinicians should assess and prevent it.
Asunto(s)
COVID-19 , Delirio , Anciano , COVID-19/complicaciones , Estudios de Cohortes , Estudios Transversales , Delirio/diagnóstico , Delirio/epidemiología , Delirio/etiología , Humanos , Unidades de Cuidados Intensivos , Estudios Prospectivos , ARN Viral , SARS-CoV-2RESUMEN
BACKGROUND/OBJECTIVE: The loss or preservation of visual imagery in patients with cortical blindness may be helpful in resolving the controversial roles assigned by some researchers to the early visual cortex during the process of visual imagery. PATIENT AND METHODS: Here we report a patient with complete permanent cortical blindness coupled with denial of the blindness (Anton syndrome) as a result of bilateral occipital infarction. RESULTS: Interestingly, the patient's ability to visualize objects, color, and spatial imagery was preserved, although cerebral computed tomography, magnetic resonance imaging, and positron emission tomography scans detected what was likely complete bilateral damage to the primary visual cortex. CONCLUSIONS: Our findings may support the hypothesis that the primary visual cortex, in which retinal spatial geometry is preserved, is not critical for visual imagery.
Asunto(s)
Ceguera Cortical/fisiopatología , Imaginación , Percepción Visual , Anciano de 80 o más Años , Ceguera Cortical/diagnóstico , Infarto Cerebral/diagnóstico , Humanos , Imagen por Resonancia Magnética , Masculino , Lóbulo Occipital/irrigación sanguínea , Lóbulo Occipital/diagnóstico por imagen , Lóbulo Occipital/patología , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos XAsunto(s)
COVID-19 , Delirio , Anciano , COVID-19/complicaciones , Delirio/etiología , Evaluación Geriátrica , HumanosRESUMEN
BACKGROUND: A common feature of Alzheimer's disease (AD) pathology is the abundance of activated microglia in neuritic plaques containing amyloid-beta protein (Abeta) and associated molecules including heparan sulfate proteoglycan (HSPG). Besides the role as pathological chaperone favouring amyloidogenesis, little is known about whether or not HSPG can induce microglial activation. Cultures of primary murine microglia were used to assess the effect of HSPG on production of proinflammatory molecules that are known to be present in neuritic plaques of AD. RESULTS: HSPG stimulated up-regulation of tumor necrosis factor-alpha (TNF-alpha), production of inducible nitric oxide synthase (iNOS) mRNA and accumulation of TNF-alpha protein and nitrite (NO2-) in a time- and concentration-dependent manner. The effects of HSPG were primarily due to the property of the protein core as indicated by the lack of microglial accumulation of TNF-alpha and NO2- in response to denaturated HSPG or heparan sulfate GAG chains (HS). CONCLUSION: These data demonstrate that HSPG may contribute to chronic microglial activation and neurodegeneration seen in neuritic plaques of AD.
RESUMEN
MCP-1 levels are increased in CSF of patients with Alzheimer's disease (AD) compared with controls, suggesting a role in the development of dementia. Recently, a biallelic A/G polymorphism in the MCP-1 promoter at position -2518 has been found, influencing the level of MCP-1 expression in response to an inflammatory stimulus. The distribution of the A-2518G SNP was determined in 269 AD patients and in 203 healthy age matched controls, showing no differences between the two groups. On the contrary, a significant increase of MCP-1 serum levels in AD patients carrying at least one G mutated allele was observed. Moreover, the highest peaks of MCP-1 serum levels were present in patients carrying two G alleles. Stratifying by ApoE genotype, gender or age at onset, no differences in both allele frequency and MCP-1 serum concentration were observed. The A-2518G polymorphism in MCP-1 gene does not seem to be a risk factor for the development of AD, but its presence correlates with higher levels of serum MCP-1, which can contribute to increase the inflammatory process occurring in AD.
Asunto(s)
Enfermedad de Alzheimer/genética , Quimiocina CCL2/genética , Quimiotaxis de Leucocito/genética , Encefalitis/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo Genético/genética , Edad de Inicio , Anciano , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/inmunología , Quimiocina CCL2/sangre , Quimiocinas/inmunología , Quimiotaxis de Leucocito/inmunología , Análisis Mutacional de ADN , Encefalitis/sangre , Encefalitis/inmunología , Femenino , Frecuencia de los Genes/genética , Pruebas Genéticas , Genotipo , Humanos , Italia , Masculino , Mutación/genética , Factores de Riesgo , Factores Sexuales , Regulación hacia Arriba/genética , Regulación hacia Arriba/inmunologíaRESUMEN
This study reports that in Schwann cell tissue culture the administration of the two pro-inflammatory cytokines, interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma), at different dosages, singly or in combination, can induce apoptosis and/or mitosis. Schwann cell apoptosis was maximal within 24 h of stimulation with 50 U/ml of IFN-gamma, while proliferation was at its peak within 24 h with 10 U/ml IL-1 beta, and both processes decreased progressively by 48 and 72 h. Moreover, the combination of the two cytokines did not show any synergistic effect. These data can be interpreted as a possible involvement of pro-inflammatory cytokines not only in myelin disruption but also in promoting remyelination.
Asunto(s)
Apoptosis , Interferón gamma/farmacología , Interleucina-1/farmacología , Células de Schwann/citología , Células de Schwann/fisiología , Animales , División Celular/efectos de los fármacos , Células Cultivadas , Combinación de Medicamentos , Mediadores de Inflamación/farmacología , Microscopía Electrónica , Ratas , Ratas Sprague-Dawley , Células de Schwann/efectos de los fármacos , Células de Schwann/ultraestructura , Factores de TiempoRESUMEN
Interferon-gamma-inducible Protein-10 (IP-10) and Monocyte Chemotactic Protein-1 (MCP-1) levels were measured by enzyme-linked immunosorbent assay (ELISA) in the CSF and in the serum from 74 patients affected by different clinical forms of Multiple Sclerosis (MS), including 39 patients with Relapsing Remitting (RR) MS in an active phase, 14 patients in a stable phase of the disease, 12 patients with Secondary Progressive (SP) MS and 9 patients with Primary Progressive (PP) MS. IP-10 and MCP-1 levels were also determined in 19 subjects with no neurological diseases or major systemic disorders, 18 patients with non-inflammatory neurological diseases, as well as in 15 patients with other inflammatory neurological diseases.IP-10 levels were significantly elevated in CSF and serum from RR and SP, but not PP-MS patients. On the contrary, MCP-1 levels were decreased in CSF and serum of all MS patients. CSF concentrations of IP-10 and MCP-1 did not significantly correlate neither with each other, nor with CSF mononuclear cell count, albumin quotient or CSF IgG index. No correlation between disease duration, clinical course or EDSS score and chemokine levels was found.IP-10 and MCP-1 undergo modifications in different subtypes of the disease: IP-10 levels in CSF and serum samples are markedly increased when inflammation is prominent, and not in PP--MS patients, where inflammation is less evident. MCP-1 decrease in CSF and serum from MS patients could be related to the regulation of T-cell polarization.
Asunto(s)
Quimiocina CCL2/líquido cefalorraquídeo , Quimiocina CXCL10/análisis , Esclerosis Múltiple Crónica Progresiva/metabolismo , Esclerosis Múltiple Recurrente-Remitente/metabolismo , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/metabolismo , Valores de ReferenciaRESUMEN
This study describes the infiltration and death of monocyte/macrophages and concomitant endoneurial expression of the pro-inflammatory cytokine interleukin-1beta (IL-1beta) and neurotrophin receptor p75 (p75NTR) in the sciatic nerve at the early phases of experimental diabetic neuropathy induced in Lewis rats by streptozotocin (STZ) intraperitoneal injection. Immunocytochemistry and single nerve fiber immunostaining showed the presence of macrophages in diabetic nerves by weeks 2 and 3 after STZ administration, and the 15% of these cells were TUNEL positive. IL-1beta was evident in scattered macrophages, and along few isolated nerve fibers until week 5, when it became undetectable, in concomitance with complete endoneurial clearance of macrophages. p75NTR showed an up-regulation in the sciatic nerve of diabetic rats that began by week 3 after STZ administration, reached its peak by week 5, and returned then to a barely detectable level by week 6. These findings seem to indicate that macrophages and IL-1beta may be involved in the pathogenesis of diabetic neuropathy, participating not only to nerve damage but also to the promotion of an attempt of regeneration via p75NTR induction.
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Neuropatías Diabéticas/fisiopatología , Interleucina-1/metabolismo , Macrófagos/fisiología , Receptores de Factor de Crecimiento Nervioso/metabolismo , Nervio Ciático/fisiopatología , Animales , Apoptosis , Muerte Celular , Movimiento Celular , Diabetes Mellitus Experimental , Neuropatías Diabéticas/patología , Inmunohistoquímica , Ratas , Ratas Endogámicas , Receptor de Factor de Crecimiento Nervioso , Nervio Ciático/patologíaRESUMEN
Monocyte chemoattractant protein-1 (MCP-1) and RANTES, as well as their related receptors, have been shown to be involved in Alzheimer's disease (AD) pathogenesis. Genes for their related receptors, CCR2 and CCR5, respectively, are characterized by the presence of two polymorphisms: a conservative change of a valine with an isoleucine at codon 64 of CCR2 (CCR2-64I) and a 32-bp deletion in the coding region of CCR5 (CCR5Delta32), which leads to the expression of a nonfunctional receptor. The distribution of the CCR2-64I and CCR5Delta32 polymorphisms was determined in 290 AD patients and in 222 controls. A decreased frequency and an absence of homozygous for the polymorphism CCR2-64I were found, thus suggesting a protective effect of the mutated allele on the occurrence of AD. However, these findings must be cautiously interpreted as the overall significance was found without adjustment for multiple comparisons and is coming from the complete absence of the genotype 64I/64I in AD patients. Conversely, no different distribution of the CCR5Delta32 deletion in the two populations was shown. Stratifying by the presence of ApoE varepsilon4 allele, gender or age at onset, no differences in either allele frequencies were observed.
Asunto(s)
Enfermedad de Alzheimer/genética , Eliminación de Gen , Polimorfismo Genético , Receptores CCR5/genética , Receptores de Quimiocina/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Apolipoproteína E4 , Apolipoproteínas E/genética , Distribución de Chi-Cuadrado , Análisis Mutacional de ADN/métodos , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Polimorfismo de Longitud del Fragmento de Restricción , ARN Mensajero/biosíntesis , Receptores CCR2 , Estudios Retrospectivos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Valina/genéticaRESUMEN
The presence of activated microglia in the spinal cord of amyotrophic lateral sclerosis (ALS) patients is usually accompanied by inflammatory biochemical changes, but these are largely unexplored. Monocyte chemoattractant protein-1 (MCP-1) is critical for recruitment of inflammatory cells of monocytic lineage after inflammation or injury to the central nervous system. MCP-1 concentrations were measured by an enzyme-linked immunosorbent assay in the cerebrospinal fluid (CSF) and the serum of 27 patients with ALS and 30 patients with noninflammatory neurological diseases. In ALS, circulating MCP-1 levels were significantly increased in the serum and particularly in the CSF. Immunoreactivity for MCP-1 in ALS spinal cord was detected mostly in astrocytes but also in microglia, neurons, and within the vasculature of the cord. Our findings suggest a role for MCP-1 as an important molecular mediator of the injury response in ALS.
Asunto(s)
Esclerosis Amiotrófica Lateral/metabolismo , Quimiocina CCL2/biosíntesis , Esclerosis Amiotrófica Lateral/patología , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Ensayo de Inmunoadsorción Enzimática , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Masculino , Microglía/metabolismo , Microglía/patología , Persona de Mediana Edad , Neuronas/metabolismo , Neuronas/patología , Índice de Severidad de la Enfermedad , Médula Espinal/metabolismo , Médula Espinal/patologíaRESUMEN
We present the case of a 58-year-old man, who has suffered from type 1 diabetes mellitus since he was young. He had monoclonal IgM kappa gammopathy of undetermined significance and high anti-MAG antibody titer. He developed a polyneuropathic picture with the clinical and laboratory features of chronic inflammatory demyelinating polyneuropathy within the span of approximately 2 years. He benefited from IV administration of high doses of immunoglobulins. Investigation of all parameters, but particularly of the clinical phenotype, can lead to a better definition of the polyneuropathic picture, especially for therapeutic and prognostic purposes.
Asunto(s)
Diabetes Mellitus Tipo 1/complicaciones , Neuropatías Diabéticas/etiología , Polineuropatías/etiología , Enfermedad Crónica , Diabetes Mellitus Tipo 1/patología , Neuropatías Diabéticas/patología , Humanos , Masculino , Persona de Mediana Edad , Polineuropatías/patologíaRESUMEN
The inducible isoform of nitric oxide synthase (iNOS), produces nitric oxide (NO) from l-arginine in response to inflammatory stimuli. NO sub-serves different functions from cytotoxicity to neuroprotection and triggers either necrosis or apoptosis. This study shows by Northern blot analysis that during experimental allergic neuritis (EAN), at the beginning of clinical signs, there is a transient extensive iNOS mRNA induction in nerve roots, in which morphology is mainly characterized by severe demyelination, but not in sciatic nerve, where scattered axonal degeneration is evident. Immunocytochemistry performed on teased nerve fibers and ultrastructural analysis showed that iNOS was localized in both inflammatory and Schwann cells, and the study of cell membrane permeability detected with fluorescent dyes showed a diffuse necrotic phenotype in the whole peripheral nervous system (PNS). With EAN clinical progression toward spontaneous recovery, endoneurial iNOS was rapidly down-regulated and in nerve roots almost all cells shifted their membrane permeability to an apoptotic phenotype, while necrosis persisted in sciatic nerve, until complete clinical recovery, when both root and nerve returned to normal. During wallerian degeneration following sciatic nerve transection, iNOS was undetectable in PNS, while endoneurial cell membrane had a diffuse necrotic phenotype. These data support the hypothesis that, during cell-mediated demyelination, iNOS may influence Schwann cell-axon relationship causing axonal damage and regulating endoneurial cell life and death.