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OBJECTIVE: Neuromodulation is a viable option for patients with drug-resistant epilepsies. We reviewed the management of patients with two deep brain neurostimulators. In addition, patients implanted with a device targeting the centromedian-parafascicular (CM-Pf) nuclear complex supplements this report to provide an illustrative case to implantation and programming a patient with three active devices. METHODS: A narrative review using PubMed and Embase identified patients with drug-resistant epilepsy implanted with more than one neurostimulator was performed. Combinations of vagus nerve stimulation (VNS), deep brain stimulation (DBS), and responsive neurostimulation (RNS) were identified. We provide a background of a newly reported case of an adult with a triple implant eventually responding to CM-Pf DBS as the third implant following suboptimal benefit from VNS and RNS. RESULTS: In review of the literature, dual-device therapy is increasing in reports of use with combinations of VNS, RNS, and DBS to treat patients with drug-resistant epilepsy. We review dual-device implants with thalamic DBS device combinations, functional neural networks, and programming patients with dual devices. CM-Pf is a new target for DBS and has shown a variable response in focal epilepsy. We report the unique case of 28-year-old male with drug-resistant focal epilepsy who experienced a 75% seizure reduction with CM-Pf DBS as his third device after suboptimal responses to VNS and RNS. After 9 months, he also experienced seizure freedom from recurrent focal to bilateral tonic-clonic seizures. No medical or surgical complications or safety issues were encountered. CONCLUSION: We demonstrate safety and feasibility in an adult combining active VNS, RNS, and CM-Pf DBS. Patients with dual-device therapy who experience a suboptimal response to initial device use at optimized settings should not be considered a neuromodulation "failure." Strategies to combine devices require a working knowledge of brain networks.
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Vascular venous malformations of the cavernous sinus have multiple imaging features that can be used to distinguish them from other entities in the region. Accurate identification of these lesions is essential: Vascular venous malformation lesions carry considerable risk of intraoperative hemorrhage, so preoperative recognition of vascular venous malformations can greatly impact the treatment strategies used. Nevertheless, because of their scarcity, many radiologists are unfamiliar with the radiologic and clinical features of cavernous sinus vascular venous malformations. This article will describe a case of an asymptomatic vascular venous malformation; outline its imaging, clinical, and pathologic features; and review the relevant literature regarding this diagnosis.
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Seno Cavernoso , Malformaciones Vasculares , Seno Cavernoso/diagnóstico por imagen , Seno Cavernoso/patología , Niño , Discapacidades del Desarrollo/patología , Humanos , Imagen por Resonancia Magnética , Malformaciones Vasculares/diagnóstico por imagen , Malformaciones Vasculares/patología , VenasRESUMEN
Optic nerve choristomas are rare entities in which a developmental focus of histologically normal tissue is abnormally located within or along a segment of the optic nerve. Although benign, choristomas may demonstrate slow growth, ultimately resulting in visual field deficits due to compression of the adjacent nerve in the few cases reported in the anterior fossa. Choristomas may have cystic components, though this has not been described in such lesions along the optic nerve. Here, a predominantly cystic optic nerve choristoma is described, with radiologic features mimicking those of an anterior cranial fossa neurenteric cyst. The case highlights the radiology-pathology correlates of choristomas and reviews the surgical approach and management of patients with such lesions.
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Coristoma/diagnóstico , Coristoma/patología , Defectos del Tubo Neural/diagnóstico , Nervio Óptico/patología , Glándulas Salivales , Coristoma/cirugía , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana EdadRESUMEN
BACKGROUND AND PURPOSE: The prevalence of patent facial nerve canals and meningoceles along the facial nerve course is unknown. This study aimed to assess the frequency of such findings in asymptomatic patients. MATERIALS AND METHODS: A retrospective review was completed of patients with high-resolution MR imaging of the temporal bone whose clinical presentations were unrelated to facial nerve pathology. Facial nerve canals were assessed for the presence of fluid along each segment and meningoceles within either the labyrinthine segment (fluid-filled distention, ≥1.0-mm diameter) or geniculate ganglion fossa (fluid-filled distention, ≥2.0-mm diameter). If a meningocele was noted, images were assessed for signs of CSF leak. RESULTS: Of 204 patients, 36 (17.6%) had fluid in the labyrinthine segment of the facial nerve canal and 40 (19.6%) had fluid in the geniculate ganglion fossa. Five (2.5%) had meningoceles of the geniculate ganglion fossa; no meningoceles of the labyrinthine segment of the canal were observed. No significant difference was observed in the ages of patients with fluid in the labyrinthine segment of the canal or geniculate ganglion compared with those without fluid (P = .177 and P = .896, respectively). Of the patients with a meningocele, one had a partially empty sella and none had imaging evidence of CSF leak or intracranial hypotension. CONCLUSIONS: Fluid within the labyrinthine and geniculate segments of the facial nerve canal is relatively common. Geniculate ganglion meningoceles are also observed, though less frequently. Such findings should be considered of little clinical importance without radiologic evidence of CSF otorrhea, meningitis, or facial nerve palsy.
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Enfermedades del Nervio Facial/epidemiología , Meningocele/epidemiología , Enfermedades del Nervio Facial/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Meningocele/diagnóstico por imagen , Prevalencia , Estudios Retrospectivos , Hueso Temporal/diagnóstico por imagenRESUMEN
INTRODUCTION: Most pituitary macroadenomas (PMA) are soft and suckable allowing transsphenoidal resection. A small percentage of PMA are firm, which significantly alters the time, technical difficulty, and effectiveness of transsphenoidal surgery. No current imaging technology can reliably assess PMA viscoelastic consistency in preparation for surgery. Magnetic resonance elastography (MRE) is an MRI-based technique that measures the propagation of mechanically induced shear waves through tissue to calculate stiffness. We prospectively evaluated MRE in 10 patients undergoing transsphenoidal resection of PMA to determine feasibility and potential usefulness. METHODS: 10 patients with PMA > 2.0 cm in maximum diameter were prospectively imaged with MRE prior to transsphenoidal surgery. Mean patient age was 59.5 ± 16.2 (22-78) years. Five were female and five male. MRE was performed with a modified single-shot spin-echo echo-planar-imaging pulse sequence on a 3T MRI. MRE values were independently calculated. The surgeon, blinded to the MRE results, graded tumor consistency at surgery as soft, intermediate, or firm. Chi-squared test compared surgical grading and MRE stiffness values. RESULTS: MRE was accomplished in all patients with excellent resolution. By surgical categorization, six tumors were soft and four intermediate. The mean MRE value for soft tumors was 1.38 ± 0.36 (1.08-1.87) kPa, while for intermediate tumors it was 1.94 ± 0.26 (1.72-2.32) kPa (p = 0.020). CONCLUSION: Determination of PMA stiffness is feasible with MRE. There was a statistically significant difference in MRE values between soft and intermediate PMAs. Further study in a larger series is ongoing to determine whether MRE will prove useful in preoperative planning for PMA.
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Adenoma/diagnóstico por imagen , Diagnóstico por Imagen de Elasticidad , Imagen por Resonancia Magnética , Neoplasias Hipofisarias/diagnóstico por imagen , Adenoma/cirugía , Adulto , Anciano , Estudios de Factibilidad , Femenino , Adenoma Hipofisario Secretor de Hormona del Crecimiento/diagnóstico por imagen , Adenoma Hipofisario Secretor de Hormona del Crecimiento/cirugía , Humanos , Hipofisectomía , Masculino , Persona de Mediana Edad , Neoplasias Hipofisarias/cirugía , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: Magnetic resonance elastography (MRE) analyzes shear wave movement through tissue to determine stiffness. In a prior study, measurements with first-generation brain MRE techniques correlated with intraoperative observations of overall meningioma stiffness. OBJECTIVE: To evaluate the diagnostic accuracy of a higher-resolution MRE technique to preoperatively detect intratumoral variations compared with surgeon assessment. METHODS: Fifteen meningiomas in 14 patients underwent MRE. Tumors with regions of distinctly different stiffness were considered heterogeneous. Intratumoral portions were considered hard if there was a significant area ≥6 kPa. A 5-point scale graded intraoperative consistency. A durometer semiquantitatively measured surgical specimen hardness. Statistics included χ, sensitivity, specificity, positive and negative predicative values, and Spearman rank correlation coefficient. RESULTS: For MRE and surgery, 9 (60%) and 7 (47%) tumors were homogeneous, 6 (40%) and 8 (53%) tumors were heterogeneous, 6 (40%) and 10 (67%) tumors had hard portions, and 14 (93%) and 12 (80%) tumors had soft portions, respectively. MRE sensitivity, specificity, and positive and negative predictive values were as follows: for heterogeneity, 75%, 100%, 100%, and 87%; for hardness, 60%, 100%, 100%, and 56%; and for softness, 100%, 33%, 86%, and 100%. Overall, 10 tumors (67%) matched well with MRE and intraoperative consistency and correlated between intraoperative observations (P = .02) and durometer readings (P = .03). Tumor size ≤3.5 cm or vascular tumors were more likely to be inconsistent (P < .05). CONCLUSION: MRE was excellent at ruling in heterogeneity with hard portions but less effective in ruling out heterogeneity and hard portions, particularly in tumors more vascular or <3.5 cm. MRE is the first technology capable of prospectively evaluating intratumoral stiffness and, with further refinement, will likely prove useful in preoperative planning.
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Diagnóstico por Imagen de Elasticidad/métodos , Neoplasias Meníngeas/diagnóstico por imagen , Neoplasias Meníngeas/cirugía , Meningioma/diagnóstico por imagen , Meningioma/cirugía , Adulto , Anciano , Encéfalo/patología , Encéfalo/cirugía , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
BACKGROUND: Subdural hematomas are not infrequent among patients with hematologic disorders as they are prone to thrombocytopenia from their disease and chemotherapy. However, rarely these patients can also have leukemic involvement of the subdural space. METHODS: Case Report with CT scan and intraoperative photographs. RESULTS: A 45-year-old woman with acute myeloid leukemia presented with progressive headache, somnolence, and hemiparesis. She was noted to be thrombocytopenic. CT scan revealed a heterodense extra-axial lesion consistent with an acute to subacute subdural hematoma. There was no antecedent trauma. After platelet transfusion, she was taken for burr hole evacuation and an opalescent pearly white mass was encountered. Pathology revealed myeloid sarcoma. CONCLUSIONS: Myeloid sarcoma can mimic subdural hematoma both clinically and radiologically. It should be considered when a patient with a prior leukemia and no antecedent trauma presents with an extra-axial lesion.
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Hematoma Subdural/diagnóstico , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Sarcoma Mieloide/diagnóstico , Diagnóstico Diferencial , Femenino , Hematoma Subdural/terapia , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Persona de Mediana Edad , Sarcoma Mieloide/patología , Sarcoma Mieloide/radioterapia , Tomografía Computarizada por Rayos XRESUMEN
In this paper we describe an initial reproducibility study of 12 proprietary compounds followed by the assessment of 51 marketed pharmaceuticals and, lastly, a summary of the data so far from 2698 proprietary compounds from the Johnson & Johnson (J&J) compound library, in the yeast GreenScreen assay (GSA). In this assay, a reporter system in the yeast cells employs the DNA damage inducible promoter of the RAD54 gene, fused to the extremely stable green fluorescent protein (GFP). The assay proved to be very robust, the Excel templates provided by Gentronix with the assay interfaced well with in-house J&J systems with little adaptation, the assay was very rapid to perform and used very little compound. The results confirm previous work which suggests that the yeast GSA detects different classes of genotoxic compounds to the Ames assay and as a result can help screen out important genotoxic compounds at the pre-regulatory test phase that are missed by Ames-test-based screens alone. A combination of SAR evaluation of genotoxicity plus an Ames-test-based screen and the GSA provides a powerful pre-regulatory test battery to aid in the selection of successful drug candidates.
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Bioensayo/métodos , Pruebas de Carcinogenicidad/métodos , Evaluación Preclínica de Medicamentos/métodos , Proteínas Fluorescentes Verdes/metabolismo , Pruebas de Mutagenicidad/métodos , Saccharomyces cerevisiae/metabolismo , Carcinógenos/farmacología , Recuento de Células , Daño del ADN/efectos de los fármacos , Genes Reporteros/genética , Proteínas Fluorescentes Verdes/genética , Reproducibilidad de los Resultados , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/genéticaRESUMEN
Nineteen coded chemicals were tested in an international collaborative study for their mutagenic activity. The assay system employed was the Ames II Mutagenicity Assay, using the tester strains TA98 and TAMix (TA7001-7006). The test compounds were selected from a published study with a large data set from the standard Ames plate-incorporation test. The following test compounds including matched pairs were investigated: cyclophoshamide, 2-naphthylamine, benzo(a)pyrene, pyrene, 2-acetylaminofluorene, 4,4'-methylene-bis(2-chloroaniline), 9,10-dimethylanthracene, anthracene, 4-nitroquinoline-N-oxide, diphenylnitrosamine, urethane, isopropyl-N(3-chlorophenyl)carbamate, benzidine, 3,3'-5,5'-tetramethylbenzidine, azoxybenzene, 3-aminotriazole, diethylstilbestrol, sucrose and methionine. The results of both assay systems were compared, and the inter-laboratory consistency of the Ames II test was assessed. Of the eight mutagens selected, six were correctly identified with the Ames II assay by all laboratories, one compound was judged positive by five of six investigators and one by four of six laboratories. All seven non-mutagenic samples were consistently negative in the Ames II assay. Of the four chemicals that gave inconsistent results in the traditional Ames test, three were uniformly classified as either positive or negative in the present study, whereas one compound gave equivocal results. A comparison of the test outcome of the different investigators resulted in an inter-laboratory consistency of 89.5%. Owing to the high concordance between the two test systems, and the low inter-laboratory variability in the Ames II assay results, the Ames II is an effective screening alternative to the standard Ames test, requiring less test material and labor.
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Cooperación Internacional , Pruebas de Mutagenicidad/normas , Mutágenos/toxicidad , Salmonella typhimurium/genéticaRESUMEN
Sixteen common seals (Phoca vitulina) were stranded on the Belgian and northern French coasts during the summer of 1998. Eleven (10 pups and one adult) were sampled for histopathological, immunohistochemical, serological, bacteriological, parasitological and virological investigations. The main gross findings were severe emaciation, acute haemorrhagic enteritis, acute pneumonia, interstitial pulmonary emphysema and oedema, and chronic ulcerative stomatitis. Microscopical lung findings were acute to subacute pneumonia with interstitial oedema and emphysema. Severe lymphocytic depletion was observed in lymph nodes. Severe acute to subacute meningoencephalitis was observed in one animal. Specific staining with two monoclonal antibodies directed against canine distemper virus (CDV) and phocine distemper virus was observed in a few lymphocytes in the spleen and lymph nodes of three seals. Anti-CDV neutralising antibodies were detected in sera from six animals. Seven of the seals were positive by reverse transcriptase-PCR for the morbillivirus phosphoprotein gene. The lesions observed were consistent with those in animals infected by a morbillivirus, and demonstrated that distemper has recently recurred in North Sea seals.
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Infecciones por Morbillivirus/veterinaria , Morbillivirus/aislamiento & purificación , ARN Viral/aislamiento & purificación , Phocidae/virología , Animales , Bélgica/epidemiología , Femenino , Francia/epidemiología , Inmunohistoquímica/veterinaria , Masculino , Morbillivirus/genética , Infecciones por Morbillivirus/epidemiología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/veterinaria , Agua de MarRESUMEN
Two immature female fin whales stranded on the Belgian and French coastlines, were examined post mortem. The main gross findings were massive parasitic infestation, associated with a large thrombus in one whale, and severe emaciation. Microscopical investigations revealed multinucleated syncytia with large intranuclear inclusion bodies in various tissues, and positive immunolabelling for morbillivirus antigens. Other evidence of morbillivirus infection was provided by the demonstration of specific viral structures in syncytia and in cell cultures, and the detection of neutralizing antibodies to canine distemper virus. To the authors>> knowledge, this is the first firm report of morbillivirus infection in baleen whales.
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Infecciones por Morbillivirus/patología , Morbillivirus/inmunología , Ballenas/virología , Animales , Antígenos Virales/análisis , Virus del Moquillo Canino/inmunología , Virus del Moquillo Focino/inmunología , Femenino , Inmunohistoquímica , Infecciones por Morbillivirus/virologíaRESUMEN
The VITOTOX test is a new bacterial genotoxicity test that was previously shown to be very rapid and sensitive. Initially only one Salmonella typhimurium strain (TA104 recN2-4) was used in the test. In this paper we introduce a second strain (TA104pr1) that can be used as an internal control to further enhance the reliability of the test. We demonstrate the usefulness of this pr1 strain in genotoxicity and toxicity testing. We also report on the results of a study where the VITOTOX test was performed on newly synthesized pharmaceutical compounds, or intermediate products in the synthesis of drug candidates. We demonstrate that the test gives identical results when performed independently in two different laboratories and that it correlates well with either the Ames test or SOS chromotest.
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Evaluación Preclínica de Medicamentos , Mutágenos/farmacología , Salmonella typhimurium/efectos de los fármacos , Pruebas de Toxicidad/métodos , Relación Dosis-Respuesta a Droga , Genes Bacterianos/genética , Mediciones Luminiscentes , Pruebas de Mutagenicidad/métodos , Reproducibilidad de los Resultados , Respuesta SOS en Genética/efectos de los fármacos , Salmonella typhimurium/genética , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
The relative efficacy of immunocytochemistry versus in situ hybridization in identifying residual beta cells was studied in rats with streptozotocin-induced diabetes. Consecutive sections of pancreas of streptozotocin-treated diabetic rats and control animals were alternately subjected to in situ hybridization (synthetic oligonucleotides complementary to rat preproinsulin mRNA) and immunocytochemistry (monoclonal antibodies to insulin). The results obtained with both methods were quantitated with the use of computer-assisted image analysis, and the ratio of cells positive by immunocytochemistry to those positive by in situ hybridization was determined. Under normoglycaemic conditions the values obtained by immunocytochemistry correlated well with those obtained by in situ hybridization (immuno/in situ > 95%). In the streptozotocin diabetic animals, however, immunocytochemistry resulted in a distinct underestimation of the number of residual beta cells (immuno/in situ < 80%). This difference was even more striking in small islet cell clusters (< 100 microns) (immuno/in situ 20%). These results suggest that in situ hybridization for prohormone mRNA is the method of choice for the identification of residual or regenerating beta cells with very low insulin content. Caution should be used when interpreting quantitative data in diabetic conditions that are based exclusively on immunocytochemical detection methods.