RESUMEN
Astroblastomas (ABs) are rare brain tumors of unknown origin. We performed an integrative genetic and epigenetic analysis of AB-like tumors. Here, we show that tumors traceable to neural stem/progenitor cells (radial glia) that emerge during early to later brain development occur in children and young adults, respectively. Tumors with MN1-BEND2 fusion appear to present exclusively in females and exhibit overexpression of genes expressed prior to 25 post-conception weeks (pcw), including genes enriched in early ventricular zone radial glia and ependymal tumors. Other, histologically classic ABs overexpress or harbor mutations of mitogen-activated protein kinase pathway genes, outer and truncated radial glia genes, and genes expressed after 25 pcw, including neuronal and astrocyte markers. Findings support that AB-like tumors arise in the context of epigenetic and genetic changes in neural progenitors. Selective gene fusion, variable imprinting and/or chromosome X-inactivation escape resulting in biallelic overexpression may contribute to female predominance of AB molecular subtypes.
Asunto(s)
Neoplasias Neuroepiteliales , Células-Madre Neurales , Linaje de la Célula/genética , Niño , Células Ependimogliales , Femenino , Humanos , Masculino , Neuroglía , Inactivación del Cromosoma X/genética , Adulto JovenRESUMEN
Circulatory arrest (CA) remains a major unresolved public health problem in the United States; the annual incidence of which is ~0.50 to 0.55 per 1000 population. Despite seminal advances in therapeutic approaches over the past several decades, brain injury continues to be the leading cause of morbidity and mortality after CA. In brief, CA typically results in global cerebral ischemia leading to delayed neuronal death in the hippocampal pyramidal cells as well as in the cortical layers. The dynamic changes occurring in neurons after CA are still unclear, and predicting these neurological changes in the brain still remains a difficult issue. It is hypothesized that the "no-flow" period produces a cytotoxic cascade of membrane depolarization, Ca2+ ion influx, glutamate release, acidosis, and resultant activation of lipases, nucleases, and proteases. Furthermore, during reperfusion injury, neuronal death occurs due to the generation of free radicals by interfering with the mitochondrial respiratory chain. The efficacy of many pharmacological agents for CA patients has often been disappointing, reflecting our incomplete understanding of this enigmatic disease. The primary obstacles to the development of a neuroprotective therapy in CA include uncertainties with regard to the precise cause(s) of neuronal dysfunction and what to target. In this review, we summarize our knowledge of the pathophysiology as well as specific cellular changes in brain after CA and revisit the most important neurofunctional, neuroimaging techniques, and serum biomarkers as potent predictors of neurologic outcome in CA patients.
Asunto(s)
Isquemia Encefálica , Señalización del Calcio , Circulación Cerebrovascular , Hipocampo , Potenciales de la Membrana , Células Piramidales , Animales , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/metabolismo , Isquemia Encefálica/fisiopatología , Isquemia Encefálica/terapia , Hipocampo/química , Hipocampo/metabolismo , Hipocampo/patología , Hipocampo/fisiopatología , Humanos , Células Piramidales/metabolismo , Daño por Reperfusión/diagnóstico , Daño por Reperfusión/metabolismo , Daño por Reperfusión/fisiopatología , Daño por Reperfusión/terapiaRESUMEN
Parathyroid carcinoma is an uncommon malignancy and a rare cause of primary hyperparathyroidism. Although this tumor is capable of metastasis, metastatic disease is very uncommon intracranially, with only seven cases reported in the literature. When intracranial metastases occur, they typically present months to years following the diagnosis of the primary tumor with hypercalcemia refractory to medical conservative treatment. Aggressive surgical resection of all metastases is necessary for control of the disease. We report a case of metastatic parathyroid carcinoma with two intracranial metastatic foci (in the left frontal lobe and left cerebellar hemisphere) identified at the time of the primary tumor diagnosis in a patient who presented with symptomatic hypercalcemia.
Asunto(s)
Neoplasias Encefálicas/secundario , Hipercalcemia/complicaciones , Neoplasias de las Paratiroides , Cerebelo/diagnóstico por imagen , Cerebelo/patología , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neoplasias de las Paratiroides/complicaciones , Neoplasias de las Paratiroides/diagnóstico , Neoplasias de las Paratiroides/patología , Tomografía de Emisión de PositronesRESUMEN
We report a case of an intraventricular tumor with features of atypical central neurocytoma with a sarcomatous component in a 44-year-old woman who presented with headaches and vomiting. Magnetic resonance imaging revealed a 3.4-cm lobulated enhancing mass in the occipital horn of the left lateral ventricle, and the patient subsequently underwent a left occipital-parietal craniotomy for debulking. The tumor contained 2 cell populations: round cells with perinuclear halos in a fibrillary background, and spindle cells with oval nuclei arranged in interlacing fascicles with focal necrosis. The round cells had diffuse synaptophysin immunopositivity, while the spindle cells were diffusely immunopositive for vimentin and had intercellular reticulin. The mitotic activity (8 mitotic figures per 10 high-power fields) and the high Ki-67 proliferation index (15.0%) were consistent with atypical central neurocytoma with a sarcomatous component. Although different histologic variants have been described, this is the first reported case, to our knowledge, of central neurocytoma with spindle cell sarcomatous features.
Asunto(s)
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patología , Diferenciación Celular , Transformación Celular Neoplásica/patología , Neurocitoma/diagnóstico , Neurocitoma/patología , Sarcoma/patología , Adulto , Neoplasias Encefálicas/terapia , Proliferación Celular , Terapia Combinada , Craneotomía , Quimioterapia , Femenino , Humanos , Imagen por Resonancia Magnética , Mitosis , Neurocitoma/terapia , Reticulina/metabolismo , Sinaptofisina/metabolismoRESUMEN
Intravascular large B-cell lymphoma (IVLBCL) is a cumbersome diagnosis to make in vivo, particularly because of its elusive nature and ability to be a relatively nonspecific 'great mimicker'. Although it frequently has skin manifestations, it often escapes diagnosis due to its angiotrophism and predilection for vessels that are difficult to biopsy (e.g., cerebral vasculature). IVLBCL can involve the vasculature of virtually any organ but typically spares the lymph nodes themselves, and likely due to defects in adhesion molecules, remains stationary in the vessels. Histologically, the malignant lymphocytes are large and mitotically active with prominent nucleoli. Immunohistochemically, the cells stain as B-cells. The disease has an overall poor prognosis. Here we present a case of IVLBCL diagnosed at autopsy that presented as a hemorrhagic frontal lobe infarct, which progressed to delirium.
Asunto(s)
Hemorragia Cerebral/diagnóstico , Infarto Cerebral/diagnóstico , Delirio/diagnóstico , Linfoma de Células B Grandes Difuso/diagnóstico , Neoplasias Vasculares/diagnóstico , Enfermedad Aguda , Anciano , Autopsia , Biopsia , Diagnóstico Diferencial , Resultado Fatal , Femenino , HumanosRESUMEN
Inflammatory processes within the central nervous system are challenging for the clinician, radiologist, and pathologist alike. They often can mimic other more well-known and defined disease processes. We present the case of a patient with a newly described inflammatory process that primarily involves the pons and adjacent structures, which is called chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). An 80-year-old man presented with numbness of his right hand that ultimately progressed to involve both lower extremities and face and was associated with mild dysarthria and ataxia. He had received the influenza vaccination 2 weeks prior. The biopsy revealed primarily reactive T-cell lymphocytic infiltrates with macrophages and gliosis. Treatment required long-term immunosuppressive therapy. CLIPPERS is a recently described central nervous system inflammatory condition that should be considered in the differential diagnosis when a prominent lymphocytic inflammatory infiltrate is encountered in brainstem, spinal cord, midbrain, or cerebellar biopsies.
Asunto(s)
Enfermedades del Sistema Nervioso Central/patología , Inmunosupresores/uso terapéutico , Vacunas contra la Influenza/efectos adversos , Puente/patología , Esteroides/uso terapéutico , Anciano de 80 o más Años , Enfermedades del Sistema Nervioso Central/tratamiento farmacológico , Humanos , Inflamación/tratamiento farmacológico , Inflamación/patología , Linfocitos , Masculino , Puente/efectos de los fármacosRESUMEN
Mutations of isocitrate dehydrogenase-1 gene (IDH1), most commonly resulting in replacement of arginine at position 132 by histidine (R132H), have been described in World Health Organization grade II and III diffuse gliomas and secondary glioblastoma. Immunohistochemistry using a mouse monoclonal antibody has a high specificity and sensitivity for detecting IDH1 R132H mutant protein in sections from formalin-fixed, paraffin-embedded tissue. Angiocentric glioma (AG), a unique neoplasm with mixed phenotypic features of diffuse glioma and ependymoma, has recently been codified as a grade I neoplasm in the 2007 World Health Organization classification of central nervous system tumors. The present study was designed to evaluate IDH1 R132H protein in AG. Three cases of AG were collected, and the diagnoses were confirmed. Expression of mutant IDH1 R132H protein was determined by immunohistochemistry on representative formalin-fixed, paraffin-embedded sections using the antihuman mouse monoclonal antibody IDH1 R132H (Dianova, Hamburg, Germany). Known IDH1 mutation-positive and IDH1 wild-type cases of grade II to IV glioma served as positive and negative controls. All 3 patients were male, aged 3, 5, and 15 years, with intra-axial tumors in the right posterior parietal-occipital lobe, right frontal lobe, and left frontal lobe, respectively. All 3 cases showed characteristic morphologic features of AG, including a monomorphous population of slender bipolar cells that diffusely infiltrated cortical parenchyma and ensheathed cortical blood vessels radially and longitudinally. All 3 cases were negative for the presence of IDH1 R132H mutant protein (0/3). All control cases showed appropriate reactivity. IDH1 R132H mutation has been described as a common molecular signature of grade II and III diffuse gliomas and secondary glioblastoma; however, AG, which exhibits some features of diffuse glioma, has not been evaluated. The absence of mutant IDH1 R132H protein expression in AG may help further distinguish this unique neoplasm from diffuse glioma.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Encefálicas/genética , Corteza Cerebral/patología , Glioma/genética , Isocitrato Deshidrogenasa/genética , Mutación Puntual , Adolescente , Astrocitoma/genética , Astrocitoma/patología , Neoplasias Encefálicas/patología , Preescolar , Ependimoma/genética , Ependimoma/patología , Marcadores Genéticos , Glioma/patología , Humanos , Masculino , Clasificación del TumorRESUMEN
With less than 50 cases previously reported in literature, angiocentric glioma (AG) is an uncommon, slow-growing tumor of the CNS that typically exhibits a low proliferative rate and is generally surgically curable. We report the case of a 3-year-old child who presented with seizures and was found to have a non-enhancing parietal lobe lesion with overlying calvarial remodeling. Following complete resection of the tumor, histopathological examination revealed bipolar spindle cells centered on cortical blood vessels, forming pseudorosettes with an ependymomatous appearance. Tumor cells were glial fibrillary acidic protein (GFAP) positive, yet failed to label with synaptophysin. Scattered tumor cells had a "dot-like" cytoplasmic staining with the antibody against epithelial membrane antigen (EMA). Collectively, these features favored a diagnosis of AG. Interestingly, the monoclonal antibody against Ki-67 (MIB-1) labeling rate averaged approximately 10.0%. The child continues to be tumor- and seizure-free ten months postoperatively. Long-term follow up is required to determine if the high proliferative rate observed in this AG translates into altered clinical behavior and/or a worse prognosis.
Asunto(s)
Neoplasias Encefálicas/diagnóstico , Glioma/diagnóstico , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/cirugía , Proliferación Celular , Preescolar , Proteína Ácida Fibrilar de la Glía/metabolismo , Glioma/metabolismo , Glioma/cirugía , Humanos , Antígeno Ki-67/metabolismo , Masculino , Mucina-1/metabolismo , Convulsiones/diagnósticoRESUMEN
Papillary tumor of the pineal region (PTPR) is a newly recognized distinct entity in the 2007 World Health Organization nomenclature. This tumor is characterized by epithelial-appearing areas with papillary features and more densely cellular areas that often display ependymal-like differentiation. Ultrastructurally, this rare neuroepithelial tumor possesses neuroendocrine, secretory, and ependymal organelles that likely originate from the subcommissural organ (SCO) near the aqueduct of Sylvius. To date, approximately fifty-seven described cases worldwide have been recognized, with ages ranging from 5 years to 66 years (mean age=32 years). Clinical presentation most often includes headache and obstructive hydrocephalus. The tumor, which is well circumscribed, may be cystic and radiographically is often considered to be consistent with the findings of a pineocytoma. Microscopic evaluation often demonstrates a lesion with papillary areas lined by epithelioid tumor cells with eosinophilic cytoplasm and more cellular areas with cells exhibiting clear or vacuolated cytoplasm. Perivascular and true rosettes may be identified. Distinctive immunohistochemical features including reactivity for keratins (AE1/AE3, CAM 5.2, CK18) and only focal GFAP staining help distinguish this neoplasm from an ependymoma. The relative paucity of data compiled for this tumor makes giving an accurate diagnosis and prognosis a daunting task. We discuss two additional cases of PTPR that presented to us within a three-month span in order to more fully elucidate the possible presentations of this rare entity. Furthermore, we examine now 59 reported cases of PTPR in order to review the current diagnostic and treatment modalities in addition to exploring emerging research encompassing this unusual neoplasm.
Asunto(s)
Neoplasias Encefálicas/patología , Carcinoma Papilar/patología , Glándula Pineal/patología , Adulto , Biomarcadores/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/cirugía , Carcinoma Papilar/metabolismo , Carcinoma Papilar/cirugía , Femenino , Humanos , Queratinas/metabolismo , Masculino , Persona de Mediana EdadRESUMEN
We report a plasma cell neoplasm in conjunction with a glioblastoma multiforme (GBM) of the conus medullaris in a 42-year-old man. Glioblastoma is a World Health Organization (WHO) grade IV neoplasm that requires surgical intervention, radiation, and possibly chemotherapy. Astrocytomas of the spinal cord are rare neoplasms, with intramedullary glioblastomas comprising only 1% to 3%. Plasma cell neoplasms result from monoclonal proliferation of mature B cells; they have been reported as a primary malignancy with gliomas arising after treatment. Secondary plasma cell neoplasms arising within glioblastomas have not previously been described. However, there have been reports of glioblastomas related to other plasma cell and hematopoietic diseases such as Waldenstrom's macroglobulinemia and myeloid sarcomas.
Asunto(s)
Glioblastoma/complicaciones , Glioblastoma/patología , Neoplasias de Células Plasmáticas/complicaciones , Neoplasias de Células Plasmáticas/patología , Neoplasias de la Médula Espinal/complicaciones , Neoplasias de la Médula Espinal/patología , Médula Espinal/patología , Adulto , Antígenos CD19/metabolismo , Proteína Ácida Fibrilar de la Glía/metabolismo , Humanos , Antígeno Ki-67/metabolismo , Imagen por Resonancia Magnética , Masculino , Necrosis , Neuroglía/metabolismo , Neuroglía/patología , Células Plasmáticas/metabolismo , Células Plasmáticas/patologíaRESUMEN
Medulloblastoma accounts for only 1% of all adult CNS tumors. Likewise, recurrence of adult medulloblastoma greater than 20 years after initial diagnosis is extremely rare.We describe a case of adult medulloblastoma with late relapse of disease. The patient was 24 years old when first diagnosed and was treated with total tumor resection and craniospinal radiation. At the age of 45, an enhancing 1.3 cm intradural extramedullary spinal cord lesion at T5 was discovered on MRI. This was presumed to be recurrent medulloblastoma in the form of drop metastasis and the patient was treated with spinal radiation. Several months following treatment, at the age of 46, a follow-up MRI demonstrated an enhancing 1.4 cm intradural extramedullary spinal cord lesion at T7. The lesion was resected and histopathologic examination was most consistent with medulloblastoma, late drop metastasis. Although rare, adult medulloblastoma recurring 20 years after initial diagnosis should always be considered in the main differential diagnosis when working up CNS lesions at or outside the primary tumor site.
Asunto(s)
Fosa Craneal Posterior/patología , Meduloblastoma/secundario , Neoplasias de la Base del Cráneo/patología , Neoplasias de la Médula Espinal/secundario , Fosa Craneal Posterior/cirugía , Humanos , Imagen por Resonancia Magnética , Masculino , Meduloblastoma/cirugía , Persona de Mediana Edad , Neoplasias de la Base del Cráneo/cirugía , Neoplasias de la Médula Espinal/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: Crystalloid fluid resuscitation after hemorrhagic shock (HS) that restores/maintains central hemodynamics often culminates in multi-system organ failure and death due to persistent/progressive splanchnic hypoperfusion and end-organ damage. Adjunctive direct peritoneal resuscitation (DPR) using peritoneal dialysis solution reverses HS-induced splanchnic hypoperfusion and improves survival. We examined HS-mediated hepatic perfusion (galactose clearance), tissue injury (histopathology), and dysfunction (liver enzymes). METHODS: Anesthetized rats were randomly assigned (n = 8/group): (1) sham (no HS); (2) HS (40% mean arterial pressure for 60 min) plus conventional i.v. fluid resuscitation (CR; shed blood + 2 volumes saline); (3) HS + CR + 30 mL intraperitoneal (IP) DPR; or (4) HS + CR + 30 mL IP saline. Hemodynamics and hepatic blood flow were measured for 2 h after CR completion. In duplicate animals, liver and splanchnic tissues were harvested for histopathology (blinded, graded), hepatocellular function (liver enzymes), and tissue edema (wet-dry ratio). RESULTS: Group 2 decreased liver blood flow, caused liver injuries (focal to submassive necrosis, zones 2 and 3) and tissue edema, and elevated liver enzymes (alanine aminotransferase (ALT), 149 +/- 28 microg/mL and aspartate aminotransferase (AST), 234 +/- 24 microg/mL; p < 0.05) compared to group 1 (73 +/- 9 and 119 +/- 10 microg/mL, respectively). Minimal/no injuries were observed in group 3; enzymes were normalized (ALT 89 +/- 9 microg/mL and AST 150 +/- 17 microg/mL), and tissue edema was similar to sham. CONCLUSIONS: CR from HS restored and maintained central hemodynamics but did not restore or maintain liver perfusion and was associated with significant hepatocellular injury and dysfunction. DPR added to conventional resuscitation (blood and crystalloid) restored and maintained liver perfusion, prevented hepatocellular injury and edema, and preserved liver function.
Asunto(s)
Hepatopatías/etiología , Hígado/irrigación sanguínea , Diálisis Peritoneal/métodos , Daño por Reperfusión/prevención & control , Resucitación/métodos , Choque Hemorrágico/complicaciones , Animales , Presión Sanguínea , Modelos Animales de Enfermedad , Galactosa/metabolismo , Frecuencia Cardíaca , Hígado/metabolismo , Hígado/patología , Hepatopatías/fisiopatología , Pruebas de Función Hepática , Masculino , Necrosis , Ratas , Ratas Sprague-Dawley , Flujo Sanguíneo Regional , Daño por Reperfusión/complicaciones , Daño por Reperfusión/terapia , Desequilibrio Hidroelectrolítico/terapiaRESUMEN
We report a papillary glioneuronal tumor occurring in the right frontal lobe of a 26-yr-old woman and we review the pertinent literature. Papillary glioneuronal tumor (PGNT) is a rare cerebral neoplasm, identified in approximately 37 cases to date. In 2007, the World Health Organization (WHO) classified the PGNT as a grade I neuronal-glial tumor because of its biphasic neurocytic and glial components and indolent clinical course. Patients commonly present with headaches or seizures, but may be asymptomatic with the mass discovered incidentally upon neuroimaging. Histology demonstrates a pseudopapillary architecture with a single or a pseudostratified layer of glial cells overlying hyalinized vasculature with interpapillary regions of neurocytic or ganglion cells. Peripheral eosinophilic granular bodies, Rosenthal fibers, hemosiderin, and areas of calcification are often noted. The PGNT displays moderate cellularity and is typically devoid of necrosis, microvascular proliferation, and mitoses. Its immunohistochemical profile includes glial fibrillary acidic protein (GFAP)-positive glial cells, synaptophysin-positive interpapillary neurocytes, and MIB-1 labeling in the range of 1-2%.
Asunto(s)
Carcinoma Papilar/patología , Glioma/patología , Adulto , Astrocitos/patología , Calcinosis/complicaciones , Calcinosis/patología , Carcinoma Papilar/complicaciones , Femenino , Lóbulo Frontal/patología , Glioma/complicaciones , Humanos , Imagen por Resonancia Magnética , Oligodendroglía/patología , Sinaptofisina/metabolismoRESUMEN
Choroid plexus carcinoma is an uncommon neoplasm of the central nervous system most commonly found in the pediatric population. It is associated with a dismal prognosis, especially if incompletely resected. Accurate histopathologic diagnosis is imperative, and this neoplasm should always be included in the differential diagnosis of a papillary intraventricular tumor. Histopathologic features include blurring of papillary architecture, layers of neoplastic choroid plexus epithelial cells with pleomorphic nuclei, increased nuclear-to-cytoplasmic ratio, increased mitotic activity, areas of necrosis, and brain invasion. Current accepted treatment is gross total surgical resection of the tumor as the goal. Use of adjuvant chemotherapy is controversial at this time; however, it is considered in some cases.
Asunto(s)
Carcinoma , Neoplasias del Plexo Coroideo , Carcinoma/patología , Carcinoma/fisiopatología , Carcinoma/cirugía , Carcinoma Papilar/patología , Neoplasias del Ventrículo Cerebral/patología , Quimioterapia Adyuvante , Plexo Coroideo/patología , Neoplasias del Plexo Coroideo/patología , Neoplasias del Plexo Coroideo/fisiopatología , Neoplasias del Plexo Coroideo/cirugía , Diagnóstico Diferencial , Células Epiteliales/patología , Humanos , Necrosis , Invasividad Neoplásica , PronósticoRESUMEN
Diploid/triploid mosaicism is an uncommon malformation syndrome thought to result from incorporation of the second polar body into a blastomere nucleus of the developing embryo. Clinical manifestations include mental and growth retardation, truncal obesity, body asymmetry, hypotonia, syndactyly, clino-/camptodactyly, malformed low-set ears, and small phallus. Although muscular atrophy has been documented in 35% of cases of diploid/triploid mosaicism, to our knowledge histologic evidence of myopathy has not been reported. We present a novel case of diploid/triploid mosaicism with evidence of central core disease and nemaline bodies (rods). The histologic and ultrastructural features are described. A review of the literature is provided, including discussion of the various theories regarding the co-expression of central cores and nemaline rods.
Asunto(s)
Anomalías Múltiples/genética , Mosaicismo , Miopatías Nemalínicas/genética , Miopatía del Núcleo Central/genética , Ploidias , Anomalías Múltiples/patología , Adenosina Trifosfatasas/metabolismo , Adulto , Femenino , Humanos , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Músculo Esquelético/fisiopatología , Miofibrillas/ultraestructura , Miopatías Nemalínicas/patología , Miopatías Nemalínicas/fisiopatología , Miopatía del Núcleo Central/patología , Miopatía del Núcleo Central/fisiopatología , Succinato Deshidrogenasa/metabolismo , SíndromeRESUMEN
PURPOSE: To evaluate the safety and tolerability of gadobenate dimeglumine (Gd-BOPTA) relative to that of gadopentetate dimeglumine (Gd-DTPA) in patients and volunteers undergoing MRI for various clinical conditions. MATERIALS AND METHODS: A total of 924 subjects were enrolled in 10 clinical trials in which Gd-BOPTA was compared with Gd-DTPA. Of these subjects, 893 were patients with known or suspected disease and 31 were healthy adult volunteers. Of the 893 patients, 174 were pediatric subjects (aged two days to 17 years) referred for MRI of the brain or spine. Safety evaluations included monitoring vital signs, laboratory values, and adverse events (AE). RESULTS: The rate of AE in adults was similar between the two agents (Gd-BOPTA: 51/561, 9.1%; Gd-DTPA: 33/472, 7.0%; P = 0.22). In parallel-group studies in which subjects were randomized to either agent, the rate of AE was 10.9% for Gd-BOPTA and 7.9% for Gd-DTPA (P = 0.21). In the subset of subjects receiving both agents in intraindividual crossover trials, the rate of AE was 8.0% for Gd-BOPTA and 8.5% for Gd-DTPA (P = 0.84). Results of other safety assessments (laboratory tests, vital signs) were similar for the two agents. CONCLUSION: The safety profile of Gd-BOPTA is similar to Gd-DTPA in patients and volunteers. Both compounds are equally well-tolerated in patients with various disease states undergoing MRI.
Asunto(s)
Ensayos Clínicos como Asunto/estadística & datos numéricos , Fiebre/etiología , Gadolinio DTPA/efectos adversos , Hemorragia/etiología , Medición de Riesgo/métodos , Vómitos/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Medios de Contraste/efectos adversos , Humanos , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Factores de Riesgo , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVES: Prospective studies and retrospective analyses were undertaken to evaluate the clinical safety of gadobenate dimeglumine (MultiHance) and to assess tolerability in special populations. MATERIALS AND METHODS: A total of 3092 subjects received MultiHance in 79 clinical trials. Data from comparisons with other contrast agents and studies in children, subjects with hepatic or renal impairment, or subjects with coronary artery disease were reviewed. Postmarketing safety surveillance data after more than 1.5 million applications were also evaluated. RESULTS: In total, 413 of 2982 (14%) adult subjects receiving MultiHance reported at least one adverse event (AE) definitely or potentially related to MultiHance, an incidence that was similar to that observed with placebo (21/127, 17%) or active controls (59/723, 8%). In crossover studies, 23 of 287 (8%) subjects receiving MultiHance experienced AE compared with 25 of 295 (9%) receiving gadopentetate dimeglumine (Magnevist). No increased AE rate was observed in children and no worsening of renal or liver function was observed in subjects with hepatic or renal impairment. No detrimental effect on cardiac electrophysiology could be observed from a retrospective analysis of ECG parameters in more than 1000 patients and healthy volunteers. The AE reporting rate from postmarketing safety surveillance of MultiHance was 0.05%. Serious AEs were rarely reported and included dyspnea, nausea, urticaria, hypotension, and anaphylactoid reactions. CONCLUSIONS: MultiHance appears to be well tolerated in adults and children and in subjects with impaired liver or kidney function or coronary artery disease. In controlled trials, MultiHance demonstrated a similar safety profile to that of Magnevist.
Asunto(s)
Sistemas de Registro de Reacción Adversa a Medicamentos , Medios de Contraste/efectos adversos , Imagen por Resonancia Magnética/efectos adversos , Meglumina/análogos & derivados , Compuestos Organometálicos/efectos adversos , Vigilancia de Productos Comercializados , Adolescente , Niño , Preescolar , Humanos , Lactante , Meglumina/efectos adversos , Seguridad , Factores de TiempoRESUMEN
Dementia with Lewy bodies (DLB) is the second most common neurodegenerative cause of dementia of the elderly following Alzheimer's disease. The significant clinical features include: fluctuating cognition with pronounced variations in attention and alertness, recurrent visual hallucinations, and spontaneous motor features of parkinsonism. As an alpha-synucleinopathy, DLB is characterized by Lewy bodies of both classical and cortical types with neuritic degeneration. This report describes an autopsy of an elderly woman with DLB and reviews the clinical and pathologic features of dementia with Lewy bodies.