RESUMEN
BACKGROUND: Allogeneic stem-cell transplantation (HSCT) is the only curative treatment in myelodysplastic syndromes (MDS). Azacitidine (AZA) is increasingly used prior to HSCT, however in Europe it is only approved for patients who are not eligible for HSCT. PATIENTS AND METHODS: We conducted a phase II multicenter study to prospectively evaluate the feasibility of HSCT after treatment with AZA in 70 patients with a myelodysplastic syndrome (MDS), 19 with acute myeloid leukemia (AML), and 8 with chronic myelomonocytic leukemia (CMML). After a median of four cycles (range 1-11): 24% of patients achieved complete remission, 14% partial remission, 8% hematologic improvement, 32% had stable and 22% progressive disease. Ten patients discontinued treatment before the planned four cycles, due to an adverse event in nine cases. RESULTS: A HSC donor was identified in 73 patients, and HSCT was performed in 54 patients (74% of patients with a donor). Main reasons for turning down HSCT were lack of a donor, an adverse event, or progressive disease (9, 12, and 16 patients, respectively). At a median follow-up of 20.5 months from enrolment, response to AZA was the only independent prognostic factor for survival. Compared to baseline assessment, AZA treatment did not affect patients' comorbidities at HSCT: the HCT-CI remained stable in 62% patients, and worsened or improved in 23% and 15% of patients, respectively. CONCLUSIONS: Our study shows that HSCT is feasible in the majority of patients with HR-MDS/AML/CMML-2 after AZA treatment. As matched unrelated donor was the most frequent source of donor cells, the time between diagnosis and HSCT needed for donor search could be 'bridged' using azacitidine. These data show that AZA prior to HSCT could be a better option than intensive chemotherapy in higher-risk MDS. The trial has been registered with the EudraCT number 2010-019673-1.
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Antimetabolitos Antineoplásicos/administración & dosificación , Azacitidina/administración & dosificación , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda/terapia , Leucemia Mielomonocítica Crónica/terapia , Síndromes Mielodisplásicos/terapia , Acondicionamiento Pretrasplante/métodos , Adulto , Anciano , Antimetabolitos Antineoplásicos/efectos adversos , Azacitidina/efectos adversos , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Esquema de Medicación , Estudios de Factibilidad , Femenino , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Italia , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/patología , Leucemia Mielomonocítica Crónica/mortalidad , Leucemia Mielomonocítica Crónica/patología , Masculino , Persona de Mediana Edad , Síndromes Mielodisplásicos/mortalidad , Síndromes Mielodisplásicos/patología , Estudios Prospectivos , Factores de Riesgo , Análisis de Supervivencia , Factores de Tiempo , Acondicionamiento Pretrasplante/efectos adversos , Acondicionamiento Pretrasplante/mortalidad , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: [18F]fluorodeoxyglucose-positron emission tomography (PET) is emerging as a strong diagnostic and prognostic tool in follicular lymphoma (FL) patients. PATIENTS AND METHODS: In a subset analysis of the FOLL05 trial (NCT00774826), we investigated the prognostic role of post-induction PET (PI-PET) scan. Patients were eligible to this study if they had a PI-PET scan carried out within 3 months from the end of induction immunochemotherapy. Progression-free survival (PFS) was the primary study end point. RESULTS: A total of 202 patients were eligible and analysed for this study. The median age was 55 years (range 33-75). Overall, PI-PET was defined as positive in 49 (24%) patients. Conventional response assessment with CT scan was substantially modified by PET: 15% (22/145) of patients considered as having a complete response (CR) after CT were considered as having partial response (PR) after PI-PET and 53% (30/57) patients considered as having a PR after CT were considered as a CR after PI-PET. With a median follow-up of 34 months, the 3-year PFS was 66% and 35%, respectively, for patients with negative and positive PI-PET (P<0.001). At multivariate analysis, PI-PET (hazard ratio 2.57, 95% confidence interval 1.52-4.34, P<0.001) was independent of conventional response, FLIPI and treatment arm. Also, the prognostic role of PI-PET was maintained within each FLIPI risk group. CONCLUSIONS: In FL patients, PI-PET substantially modifies response assessment and is strongly predictive for the risk of progression. PET should be considered in further updates of response criteria.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Fluorodesoxiglucosa F18 , Linfoma Folicular/diagnóstico por imagen , Radiofármacos , Supervivencia sin Enfermedad , Femenino , Humanos , Quimioterapia de Inducción , Estimación de Kaplan-Meier , Linfoma Folicular/tratamiento farmacológico , Linfoma Folicular/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Tomografía de Emisión de Positrones , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVES: Chronic cerebrospinal venous insufficiency (CCSVI) is associated with multiple sclerosis (MS). The objective of the study was to see if percutaneous transluminal angioplasty (PTA) of duplex-detected lesions, of the internal jugular and/or azygous veins, was safe, burdened by a significant restenosis rate, and whether there was any evidence that treatment reduced MS disease activity. DESIGN: This was a case-control study. MATERIALS: We studied 15 patients with relapsing-remitting MS and duplex-detected CCSVI. METHODS: Eight patients had PTA in addition to medical therapy (immediate treatment group (ITG)), whereas seven had treatment with PTA after 6 months of medical therapy alone (delayed treatment group (DTG)). RESULTS: No adverse events occurred. At 1 year, there was a restenosis rate of 27%. Overall, PTA was followed by a significant improvement in functional score compared with baseline (p < 0.02). The annualised relapse rate was 0.12% in the ITG compared with 0.66% in the DTG (p = NS). Magnetic resonance imaging (MRI) blindly demonstrates a trend for fewer T2 lesions in the ITG (p = 0.081), corresponding to a 10% decrease in the ITG compared with a 23% increase in the DTG over the first 6 months of the study. CONCLUSIONS: This study further confirms the safety of PTA treatment in patients with CCSVI associated with MS. The results, despite the significant rate of restenosis, are encouraging and warrant a larger multicentre double-blinded, randomised study.
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Angioplastia de Balón , Vena Ácigos , Venas Yugulares , Esclerosis Múltiple Recurrente-Remitente/terapia , Médula Espinal/irrigación sanguínea , Enfermedades Vasculares/terapia , Insuficiencia Venosa/terapia , Adulto , Angioplastia de Balón/efectos adversos , Vena Ácigos/diagnóstico por imagen , Estudios de Casos y Controles , Enfermedad Crónica , Constricción Patológica , Medicina Basada en la Evidencia , Femenino , Humanos , Italia , Venas Yugulares/diagnóstico por imagen , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/diagnóstico , Esclerosis Múltiple Recurrente-Remitente/etiología , New York , Proyectos Piloto , Recurrencia , Factores de Tiempo , Resultado del Tratamiento , Ultrasonografía Doppler Dúplex , Enfermedades Vasculares/complicaciones , Enfermedades Vasculares/diagnóstico , Insuficiencia Venosa/diagnóstico , Insuficiencia Venosa/etiología , Adulto JovenRESUMEN
BACKGROUND AND AIMS: Rare (611C) and common (1062V) variants of the Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6) display reduced activation of Wnt/ß-catenin signaling. The rare gene variant was associated with hypertension, metabolic abnormalities, and early coronary artery disease. We investigated whether the common 1062V LRP6 variant was related to carotid artery atherosclerosis (CAA) in hypertensive patients. METHODS AND RESULTS: Retrospective study of 334 hypertensive patients (<65 years old) who underwent carotid artery ultrasonography. Hypertension, type 2 diabetes, dyslipidemia, glomerular filtration rate, and smoking habit were evaluated. CAA was defined by the presence of atherosclerotic plaques (focal intima-media thickness ≥ 1.3 mm). Logistic regression models were used to estimate the independent effect of 1062V allele. The relationship between LRP6 genotypes and LRP6 gene expression in carotid plaques was also investigated. No difference was observed between genotypes in clinical variables except for a slightly higher fasting glucose in 1062V carriers. The 1062V LRP6 variant was an independent risk factor for CAA in both unadjusted (OR 2.08, 95%CI 1.27-3.41, p=0.003) and adjusted models (OR 1.92, 95%CI 1.09-3.39, p=0.02). LRP6 was expressed in carotid atherosclerotic plaques at significantly lower levels (p=0.015) in 1062V carriers. CONCLUSION: Beside the role of established risk factors, 1062V variant of LRP6 and CAA are strongly associated in hypertensive patients, making LRP6 a novel relevant candidate gene for atherosclerosis in the presence of hypertension.
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Enfermedades de las Arterias Carótidas/genética , Hipertensión/genética , Proteínas Relacionadas con Receptor de LDL/genética , Proteínas Relacionadas con Receptor de LDL/metabolismo , Adulto , Enfermedades de las Arterias Carótidas/metabolismo , Femenino , Expresión Génica , Humanos , Hipertensión/metabolismo , Modelos Logísticos , Proteína-6 Relacionada a Receptor de Lipoproteína de Baja Densidad , Masculino , Persona de Mediana Edad , Placa Aterosclerótica/metabolismo , Estudios Retrospectivos , Factores de Riesgo , Transducción de Señal , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , beta Catenina/genética , beta Catenina/metabolismoRESUMEN
OBJECTIVE: To verify whether the finding of denervation activity on EMG at the time of diagnosis has a prognostic value in amyotrophic lateral sclerosis (ALS). METHODS: We retrospectively studied all the patients discharged with a diagnosis of ALS between January 2009 and January 2017. 92 patients met the inclusion criteria. We mainly verified three prognostic targets:All EMG examinations were reviewed and a denervation score (DS) was calculated. The association of DS with clinical milestones was analysed, adjusting for disease duration, age , sex, and clinical phenotype. RESULTS: We found a significant association between bulbar DS and time to NIV/tracheostomy (HR: 3.34, 95% CI: 1.49 to 7.48, p = 0.002) and with survival (HR 3.633, 95% CI 1.681-7.848, p = 0.001), regardless of the clinical phenotype. Furthermore, we found a significant influence of a general DS on survival (HR: 2.62, 95% CI 1.335-5.160, p = 0.005). CONCLUSION: EMG assessment could be of value not just for ALS diagnosis but also for its intrinsic prognostic value. SIGNIFICANCE: EMG could provide additional information about the rate of progression of ALS as early as the diagnosis is made.
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Esclerosis Amiotrófica Lateral/diagnóstico , Electromiografía/métodos , Anciano , Electromiografía/normas , Femenino , Fuerza de la Mano , Humanos , Masculino , Persona de Mediana Edad , Neuronas Motoras/fisiología , Músculo Esquelético/inervación , Músculo Esquelético/fisiología , Fenotipo , Ventilación Pulmonar , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The extracranial venous outflow routes in clinically defined multiple sclerosis (CDMS) have not previously been investigated. METHODS: Sixty-five patients affected by CDMS, and 235 controls composed, respectively, of healthy subjects, healthy subjects older than CDMS patients, patients affected by other neurological diseases and older controls not affected by neurological diseases but scheduled for venography (HAV-C) blindly underwent a combined transcranial and extracranial colour-Doppler high-resolution examination (TCCS-ECD) aimed at detecting at least two of five parameters of anomalous venous outflow. According to the TCCS-ECD screening, patients and HAV-C further underwent selective venography of the azygous and jugular venous system with venous pressure measurement. RESULTS: CDMS and TCCS-ECD venous outflow anomalies were dramatically associated (OR 43, 95% CI 29 to 65, p<0.0001). Subsequently, venography demonstrated in CDMS, and not in controls, the presence of multiple severe extracranial stenosis, affecting the principal cerebrospinal venous segments; this provides a picture of chronic cerebrospinal venous insufficiency (CCSVI) with four different patterns of distribution of stenosis and substitute circle. Moreover, relapsing-remitting and secondary progressive courses were associated with CCSVI patterns significantly different from those of primary progressive (p<0.0001). Finally, the pressure gradient measured across the venous stenosies was slightly but significantly higher. CONCLUSION: CDMS is strongly associated with CCSVI, a scenario that has not previously been described, characterised by abnormal venous haemodynamics determined by extracranial multiple venous strictures of unknown origin. The location of venous obstructions plays a key role in determining the clinical course of the disease.
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Trastornos Cerebrovasculares/etiología , Esclerosis Múltiple/complicaciones , Enfermedades de la Médula Espinal/etiología , Columna Vertebral/irrigación sanguínea , Adulto , Trastornos Cerebrovasculares/diagnóstico por imagen , Trastornos Cerebrovasculares/fisiopatología , Enfermedad Crónica , Constricción Patológica , Progresión de la Enfermedad , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/fisiopatología , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Esclerosis Múltiple Recurrente-Remitente/fisiopatología , Postura/fisiología , Flujo Sanguíneo Regional/fisiología , Enfermedades de la Médula Espinal/diagnóstico por imagen , Enfermedades de la Médula Espinal/fisiopatología , Columna Vertebral/diagnóstico por imagen , Posición Supina/fisiología , Ultrasonografía Doppler en Color , Ultrasonografía Doppler TranscranealRESUMEN
OBJECTIVE: To define the temporal evolution of intrinsic tissue damage and atrophy in the cervical cord and the brain portion of the corticospinal tracts (CST) from patients with amyotrophic lateral sclerosis (ALS). METHODS: Conventional and diffusion tensor (DT) magnetic resonance imaging (MRI) of the cervical cord and brain were obtained from 17 ALS patients and 20 controls, at baseline and after a mean follow-up of 9 months. The following measurements were assessed: (a) cervical cord cross-sectional area, average mean diffusivity (MD) and average fractional anisotropy (FA); and (b) CST T2-visible hyperintensities, average MD and FA. RESULTS: During the follow-up, ALS patients showed a significant decrease in cord area (p = 0.003) and cord average FA (p = 0.01), and a significant increase in cord average MD (p = 0.01). In ALS patients, longitudinal changes of diffusivity measurements were not associated with cord area changes. At baseline, brain CST average MD was significantly higher in ALS patients compared with controls (p = 0.001). Brain CST diffusivity measurements remained stable over time in ALS patients and did not correlate with cord damage. CONCLUSIONS: This study shows that progressive tissue loss and injury to the remaining tissue occur in the cervical cord of ALS patients and that these two features of ALS-related pathology are not strictly interrelated. Cord pathology in ALS patients is likely to be independent of brain changes, indicating that imaging the cervical cord may be a useful adjunctive tool to monitor ALS evolution.
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Esclerosis Amiotrófica Lateral/patología , Imagen de Difusión por Resonancia Magnética , Tractos Piramidales/patología , Adulto , Anciano , Anisotropía , Atrofia , Vértebras Cervicales , Femenino , Estudios de Seguimiento , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Neuronas Motoras/patología , Degeneración Nerviosa/patologíaRESUMEN
OBJECTIVE: To investigate potential associations between A-13G and G79A polymorphisms of the protein Z gene and venous thrombosis and other clinical manifestations in Italian patients with Behçet's disease (BD). METHODS: 176 Italian patients who satisfied the International Study Group criteria for BD and 134 healthy age- and sex- matched blood donors were genotyped for A-13G and G79A polymorphisms of the protein Z gene by molecular methods. 113 and 112 of the 176 BD patients were also genotyped for factor V Leiden and prothrombin gene G20210A polymorphisms. Serological HLA class B51 typing was performed by a standard microlymphocytotoxicity technique. The patients were subgrouped according to the presence or absence of clinical manifestations. RESULTS: The distribution of allele and genotype frequencies of A-13G and G79A polymorphisms did not differ significantly between BD patients and healthy controls.The frequencies of carriage rates of protein Z G79A and A-13G polymorphisms in BD patients with and without DVT were similar. Similarly, no associations between thrombotic events and the protein Z gene polymorphisms studied were observed in BD patients carrying factor V Leiden or prothrombin gene G20210A mutations. No significant associations were observed between protein Z polymorphisms and the occurrence of specific clinical findings. CONCLUSION: No association between DVT and A-13G or G79A polymorphisms of the protein Z gene was found in Italian BD patients. Furthermore, these protein Z polymorphisms in BD do not seem to increase the risk of DVT due to factor V Leiden or prothrombin gene G20210A mutations.
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Síndrome de Behçet/genética , Proteínas Sanguíneas/genética , Intrones/genética , Polimorfismo de Nucleótido Simple , Trombosis de la Vena/genética , Adulto , Estudios de Casos y Controles , Factor V/genética , Femenino , Humanos , Italia , Masculino , Protrombina/genética , Adulto JovenRESUMEN
OBJECTIVE: To investigate potential associations between toll-like receptor 4 (TLR4) gene polymorphisms and susceptibility to, clinical features, and severity of Behçet's disease (BD). METHODS: A total of 189 Italian patients who satisfied the International Study Group criteria for BD and 210 healthy age- and sex-matched blood donors were genotyped for two coding single nucleotide polymorphisms of TLR4 (Asp299Gly and Thr399Ile) by molecular methods. The patients were subgrouped according to the presence or absence of clinical manifestations. Severity score was calculated. RESULTS: The distribution of allele and genotype frequencies did not differ significantly between the BD patients and the healthy controls. No significant associations were found when BD patients with and those without clinical manifestations were compared. No association between TLR4 polymorphisms and severity score was observed. CONCLUSION: Our data suggest that the TLR4 gene polymorphisms are not associated with susceptibility to, clinical expression of, and severity of BD in Italian patients.
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Síndrome de Behçet/genética , Polimorfismo de Nucleótido Simple , Receptor Toll-Like 4/genética , Adulto , Estudios de Casos y Controles , Femenino , Genotipo , Humanos , Italia , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Chronic cerebrospinal venous insufficiency (CCSVI) is a vascular picture that shows a strong association with multiple sclerosis (MS). The aim of this study was to investigate the relationship between a Doppler cerebral venous hemodynamic insufficiency severity score (VHISS) and cerebrospinal fluid (CSF) flow dynamics in 16 patients presenting with CCSVI and relapsing-remitting MS (CCSVI-MS) and in eight healthy controls (HCs). The two groups (patients and controls) were evaluated using validated echo-Doppler and advanced 3T-MRI CSF flow measures. Compared with the HCs, the CCSVI-MS patients showed a significantly lower net CSF flow (p=0.027) which was highly associated with the VHISS (r=0.8280, r2=0.6855; p=0.0001). This study demonstrates that venous outflow disturbances in the form of CCSVI significantly impact on CSF pathophysiology in patients with MS.
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Líquido Cefalorraquídeo/fisiología , Circulación Cerebrovascular/fisiología , Trastornos Cerebrovasculares/complicaciones , Hemodinámica , Esclerosis Múltiple Recurrente-Remitente/complicaciones , Insuficiencia Venosa/complicaciones , Adulto , Encéfalo/irrigación sanguínea , Estudios de Casos y Controles , Presión del Líquido Cefalorraquídeo , Trastornos Cerebrovasculares/líquido cefalorraquídeo , Enfermedad Crónica , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Análisis por Apareamiento , Esclerosis Múltiple Recurrente-Remitente/líquido cefalorraquídeo , Proyectos Piloto , Valores de Referencia , Flujo Sanguíneo Regional , Índice de Severidad de la Enfermedad , Método Simple Ciego , Médula Espinal/irrigación sanguínea , Ultrasonografía Doppler en Color , Ultrasonografía Doppler Transcraneal , Insuficiencia Venosa/líquido cefalorraquídeoRESUMEN
OBJECTIVE: Cardiovascular peptides such as angiotensin II (Ang II) and atrial natriuretic peptide (ANP) have metabolic effects on adipose cells. These peptides might also regulate adipocyte proliferation and visceral adipose tissue (VAT) expansion. Well-differentiated and stabilized primary cultures of human visceral mature adipocytes (MA) and in vitro-differentiated preadipocytes (DPA) were used as a model to study regulation of VAT expansion. METHODS: Adipocyte differentiation was evaluated by Oil Red O staining and antiperilipin antibodies. MA and DPA from intra- and retro-peritoneal depots were treated with increasing Ang II (with or without valsartan, a highly selective, competitive, 'surmountable' AT1 antagonist devoid of peroxisome proliferator-activated receptor gamma agonistic activity) or ANP concentrations. Cell counts and bromodeoxyuridine incorporation were used to evaluate proliferation. Apoptosis was evaluated by Hoechst 33342 staining. 8-Bromo cyclic guanosine monophosphate (8Br-cGMP) was used to investigate ANP effects, and real-time PCR to evaluate Ang II and ANP receptors' expression. RESULTS: Cell proliferation was progressively stimulated by increasing Ang II concentrations (starting at 10-11 M) and inhibited by ANP (already at 10-13 M) in both MA and DPA. Co-incubation with increasing Ang II concentrations and valsartan indicated that Ang II effects were AT1-mediated. Indeed, AT2 receptors were not expressed. Valsartan alone slightly inhibited basal proliferation indicating an autocrine/paracrine growth factor-like effect of endogenous, adipocyte-derived Ang II. 8Br-cGMP experiments indicated that the effects of ANP were mediated by the guanylyl cyclase type A receptor. CONCLUSION: A cell-culture model to study VAT growth showed stimulation by Ang II and inhibition by ANP at physiological concentrations. Because similar effects are likely to occur in vivo, Ang II and ANP might be important modulators of VAT expansion and associated metabolic and cardiovascular consequences.
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Adipocitos/efectos de los fármacos , Tejido Adiposo/efectos de los fármacos , Angiotensina II/farmacología , Factor Natriurético Atrial/farmacología , Grasa Intraabdominal/efectos de los fármacos , Adipocitos/citología , Tejido Adiposo/citología , Adulto , Anciano , Anciano de 80 o más Años , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Femenino , Humanos , Grasa Intraabdominal/citología , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: Neuropathological descriptions of the brain in Friedreich's ataxia (FRDA) were obtained before availability of the current molecular genetic tests for this disease. Voxel-based morphometry (VBM) enables an unbiased whole-brain quantitative analysis of differences in gray matter (GM) and white matter (WM) volume. METHODS: Using VBM, we assessed the brain structural damage in 22 patients with genetically confirmed FRDA and 25 healthy controls. The results were correlated with the disease duration and the severity of the patients' clinical deficits--evaluated using the International Cerebellar Ataxia Rating Scale and Inherited Ataxia Clinical Rating Scale. RESULTS: In patients with FRDA, VBM showed a symmetrical volume loss in dorsal medulla, infero-medial portions of the cerebellar hemispheres, the rostral vermis and in the dentate region. No volume loss in cerebral hemispheres was observed. The atrophy of the cerebellum and medulla correlated with the severity of the clinical deficit and disease duration. CONCLUSIONS: In patients with FRDA, significant GM and WM loss was observed only in the cerebellum and dorsal medulla. These structural changes correlate with the severity of the clinical deficit and disease duration.
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Encéfalo/anatomía & histología , Encéfalo/fisiopatología , Ataxia de Friedreich/diagnóstico , Ataxia de Friedreich/fisiopatología , Adolescente , Adulto , Anciano , Alelos , Atrofia/patología , Atrofia/fisiopatología , Cerebelo/patología , Cerebelo/fisiopatología , Giro Dentado/patología , Giro Dentado/fisiopatología , Evaluación de la Discapacidad , Progresión de la Enfermedad , Femenino , Ataxia de Friedreich/genética , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with severe cervical cord damage due to degeneration of the corticospinal tracts and loss of lower motor neurones. Diffusion tensor magnetic resonance imaging (DT MRI) allows the measurement of quantities reflecting the size (such as mean diffusivity) and orientation (such as fractional anisotropy) of water-filled spaces in biological tissues. METHODS: Mean diffusivity and fractional anisotropy histograms from the cervical cord of patients with ALS were obtained to: (1) quantify the extent of tissue damage in this critical central nervous system region; and (2) investigate the magnitude of the correlation of cervical cord DT MRI metrics with patients' disability and tissue damage along the brain portion of the corticospinal tracts. Cervical cord and brain DT MRI scans were obtained from 28 patients with ALS and 20 age-matched and sex-matched controls. Cord mean diffusivity and fractional anisotropy histograms were produced and the cord cross-sectional area was measured. Average mean diffusivity and fractional anisotropy along the brain portion of the corticospinal tracts were also measured. RESULTS: Compared with controls, patients with ALS had significantly lower mean fractional anisotropy (p = 0.002) and cord cross-sectional area (p<0.001). Mean diffusivity histogram-derived metrics did not differ between the two groups. A strong correlation was found between mean cord fractional anisotropy and the ALS Functional Rating Score (r = 0.74, p<0.001). Mean cord and brain fractional anisotropy values correlated moderately (r = 0.37, p = 0.05). CONCLUSIONS: Cervical cord DT MRI in patients with ALS allows the extent of cord damage to be graded. The conventional and DT MRI changes found are compatible with the presence of neuroaxonal loss and reactive gliosis, with a heterogeneous distribution of the pathological process between the brain and the cord. The correlation found between cord fractional anisotropy and disability suggests that DT MRI may be a useful adjunctive tool to monitor the evolution of ALS.
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Esclerosis Amiotrófica Lateral/complicaciones , Encéfalo/patología , Imagen de Difusión por Resonancia Magnética , Evaluación de la Discapacidad , Tractos Piramidales/patología , Adulto , Anciano , Anisotropía , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Magnetic resonance (MR) techniques enable in vivo measurement of the atrophy of the brainstem and cerebellum in spinocerebellar ataxia type 1 (SCA1) and 2 (SCA2) patients, which is accompanied by a decrease in the concentration of N-acetyl aspartate (NAA) or of the NAA/creatine ratio in the pons and cerebellum. Mean diffusivity (D) is emerging as an additional sensitive and quantitative MR parameter to investigate brain diseases. In order to explore differences between the MR features of SCA1 and SCA2 and correlate the MR and clinical findings in the two conditions, we examined 16 SCA1 patients, 12 SCA2 patients and 20 healthy control subjects. The MR protocol included T1-weighted 3D gradient echo sequences, single-voxel proton spectroscopy of the right cerebellar hemisphere (dentate and peridentate region) and of the pons with a PRESS sequence and an external reference quantitation method, and (in nine patients with SCA1 and nine patients with SCA2) diffusion-weighted echo-planar images with reconstruction of the D maps. The patients were evaluated with the Inherited Ataxia Clinical Rating Scale (IACRS). Compared with control subjects, the SCA1 and SCA2 patients showed a decrease (P < 0.01) in the volume of the brainstem and cerebellum and in the concentration of NAA in the pons and cerebellar hemisphere, whereas D of the brainstem and cerebellum was increased. No significant difference was observed between the SCA1 and SCA2 patient groups. No correlation between cerebellar volume and dentate and peridentate NAA concentration was found in SCA1 or SCA2 patients. The volume of the brainstem, D of the brainstem and cerebellum and the concentration of NAA in the pons were correlated (P < 0.05) with the IACRS score in SCA1 but not in SCA2. This discrepancy is in line with the clinical observation that the clinical deficit has a later onset and faster progression in SCA1 and an earlier onset and slower progression in SCA2, and suggests that neurodegeneration of the brainstem is a comparatively more rapid process in SCA1. In conclusion, our study indicates that SCA1 and SCA2 substantially exhibit the same MR features. The correlation in SCA1 between clinical severity and quantitative volumetric, diffusion MRI and proton MR spectroscopy findings in the brainstem indicates that these measurements might be employed for longitudinal studies and hopefully as surrogate markers in future pharmacological trials of this condition.
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Ácido Aspártico/análogos & derivados , Tronco Encefálico/patología , Ataxias Espinocerebelosas/patología , Adulto , Anciano , Ácido Aspártico/metabolismo , Biomarcadores/análisis , Tronco Encefálico/metabolismo , Cerebelo/metabolismo , Cerebelo/patología , Creatina/metabolismo , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética , Masculino , Persona de Mediana Edad , Puente/metabolismo , Índice de Severidad de la Enfermedad , Ataxias Espinocerebelosas/metabolismo , Ataxias Espinocerebelosas/fisiopatologíaRESUMEN
OBJECTIVES: To study the ultrastructure of intraluminal defects found in the internal jugular vein by using a scanning electron microscopy. METHODS: Using a scanning electron microscopy, intraluminal septa and/or defective valves blocking the flow in the distal internal jugular vein of seven patients were studied together with the adjacent wall and compared with control specimen. RESULTS: The internal jugular veins' wall showed a significant derangement of the endothelial layer as compared to controls. Surprisingly, no endothelial cells were found in the defective cusps, and the surface of the structure is covered by a fibro-reticular lamina. CONCLUSIONS: Although the lack of endothelial cells in the internal jugular vein intraluminal obstacles is a further abnormality found in course of chronic cerebrospinal venous insufficiency, our investigation cannot clarify whether this finding is primary or caused by progressive loss of endothelium in relation to altered haemodynamic forces and/or to a past post-thrombotic/inflammatory remodelling.
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Venas Yugulares/ultraestructura , Insuficiencia Venosa/fisiopatología , Válvulas Venosas/diagnóstico por imagen , Adulto , Anciano , Enfermedad Crónica , Femenino , Voluntarios Sanos , Hemodinámica , Humanos , Inflamación , Masculino , Microscopía Electrónica de Rastreo , Persona de Mediana Edad , Esclerosis Múltiple/complicaciones , Perfusión , Tomografía Computarizada de Emisión de Fotón Único , Ultrasonografía Doppler en Color , Insuficiencia Venosa/complicacionesRESUMEN
Thirty-one patients with severe drug-resistant epilepsy entered the study. Vigabatrin (2 to 3 g/d, stratified according to weight) and placebo were administered orally, as add-on therapy in random order under double-blind conditions, each for three months using a crossover design. Thirty patients completed both periods. Of these, ten patients (33%) showed a decrease in seizure frequency of 50% or more. In the 15 patients presenting with complex partial seizures, "temporal" electroencephalographic abnormalities, and relatively low seizure frequency, there was a significant reduction in seizure frequency during vigabatrin treatment. No significant treatment effect was found for the remaining 15 patients, who presented with mixed seizure types, multifocal electroencephalographic abnormalities, and high seizure frequencies. Tolerability to vigabatrin was good; the most frequently reported unwanted effect was drowsiness. Plasma concentrations of phenytoin showed a significant reduction during the vigabatrin period. The results demonstrate the efficacy and good tolerability of vigabatrin therapy in patients with severe complex partial epilepsy.
Asunto(s)
Aminocaproatos/uso terapéutico , Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Adolescente , Adulto , Aminocaproatos/efectos adversos , Ansiolíticos/uso terapéutico , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/sangre , Benzodiazepinas , Niño , Método Doble Ciego , Interacciones Farmacológicas , Resistencia a Medicamentos , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , VigabatrinRESUMEN
We analyzed electroencephalographic (EEG) activity and spatial distribution of the pattern-reversal visual evoked potential (PVEP) in 20 patients with unilateral lesions in the retrochiasmal visual pathways. Focal abnormalities that were consistent with lesion location were present in the topographically analyzed EEG or VEP of 85% of the patients, compared with a 70% detection rate for conventional analysis techniques. Quantitative analysis of spectrally analyzed EEG revealed focal abnormality in 7 patients whose conventional EEG was interpreted as either normal or diffusely slow. However, focal paroxysmal spikes present in the EEG of 1 patient were missed by EEG mapping, and a false localization of quantitative EEG abnormality contralateral to the lesion occurred in 1 patient. Topographic analysis of the PVEP was no more sensitive to retrochiasmatic lesions than conventional analysis of 2 lateral occipital electrodes. We conclude that topographic mapping is a valid technique in the detection of localized cerebral lesions.
Asunto(s)
Hemianopsia/fisiopatología , Adulto , Anciano , Electroencefalografía , Electrofisiología , Potenciales Evocados Visuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Estimulación Luminosa/métodos , Campos VisualesRESUMEN
We studied 58 patients with partial or generalized epilepsy who had transcranial magnetic stimulation (TMS) of the brain motor regions. Short-term monitoring disclosed that the stimulation did not provoke seizures or EEG changes in any patient. Long-term follow-up disclosed that the epileptic condition was not made worse by TMS. TMS, as currently used for monitoring conduction in central motor pathways, does not induce seizures in drug-treated epileptic patients.
Asunto(s)
Epilepsias Parciales/terapia , Estimulación Magnética Transcraneal/métodos , Adulto , Electroencefalografía , Epilepsias Parciales/fisiopatología , Femenino , Humanos , Masculino , Monitoreo Fisiológico , Convulsiones/fisiopatología , Convulsiones/terapia , Factores de TiempoRESUMEN
MRI showed impingement of the vertebral artery on the left lateral medulla in two patients with arterial hypertension, exaggerated startle reflexes (hyperekplexia), and progressive spastic paresis. One patient underwent microvascular decompression with normalization of arterial hypertension, disappearance of hyperekplexia, and improvement of spastic paresis. The combination of arterial hypertension, hyperekplexia, and progressive spastic paresis should arouse suspicion of neurovascular compression of the lateral medulla.