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2.
BMC Neurol ; 21(1): 231, 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34162346

RESUMO

BACKGROUND: Gliosarcoma (GS) refers to the presence of mesenchymal differentiation (as seen using light microscopy) in the setting of glioblastoma (GB, an astrocytoma, WHO Grade 4). Although the same approach to treatment is typically adopted for GS and GB, there remains some debate as to whether GS should be considered a discrete pathological entity. Differences between these tumors have not been clearly established at the molecular level. METHODS: Patients with GS (n=48) or GB (n=1229) underwent molecular profiling (MP) with a pan-cancer panel of tests as part of their clinical care. The methods employed included next-generation sequencing (NGS) of DNA and RNA, copy number variation (CNV) of DNA and immunohistochemistry (IHC). The MP comprised 1153 tests in total, although results for each test were not available for every tumor profiled. We analyzed this data retrospectively in order to determine if our results were in keeping with what is known about the pathogenesis of GS by contrast with GB. We also sought novel associations between the MP and GS vs. GB which might improve our understanding of pathogenesis of GS. RESULTS: Potentially meaningful associations (p<0.1, Fisher's exact test (FET)) were found for 14 of these tests in GS vs. GB. A novel finding was higher levels of proteins mediating immuno-evasion (PD-1, PD-L1) in GS. All of the differences we observed have been associated with epithelial-to-mesenchymal transition (EMT) in other tumor types. Many of the changes we saw in GS are novel in the setting of glial tumors, including copy number amplification in LYL1 and mutations in PTPN11. CONCLUSIONS: GS shows certain characteristics of EMT, by contrast with GB. Treatments targeting immuno-evasion may be of greater therapeutic value in GS relative to GB.


Assuntos
Glioblastoma/patologia , Gliossarcoma/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Variações do Número de Cópias de DNA , Transição Epitelial-Mesenquimal , Feminino , Glioblastoma/genética , Glioblastoma/metabolismo , Gliossarcoma/genética , Gliossarcoma/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteína Tirosina Fosfatase não Receptora Tipo 11/genética , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Estudos Retrospectivos , Adulto Jovem
3.
Open Access J Clin Trials ; 12: 1-13, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32123490

RESUMO

With the general population reaching higher ages, a surge in Alzheimer's disease (AD) incidence will happen in the coming decades, putting a heavy burden on families and healthcare systems Worldwide. This emphasizes the pressing need for AD therapeutic interventions. Accumulating evidence indicates that inflammation is prominent both in the blood and central nervous system of AD sufferers. These data suggest that systemic inflammation plays a crucial role in the cause and effects of AD neuropathology. Capitalizing on our experience from a previous clinical trial with thalidomide, we hypothesize that modulating inflammation via the pleiotropic immunomodulator lenalidomide may alter AD if administered during a proper time window in the course of the disease. Thus, in this Phase II, proof-of mechanism study, 30 amnestic mild cognitive impairment (aMCI) subjects will be treated with lenalidomide at 10 mg/day for 12 months on a 1:1 ratio, followed by a 6 months washout period. The primary objective of this study is to investigate the effect of lenalidomide on cognition, which is assessed at regular intervals. The secondary objective is to assess the safety and tolerability of lenalidomide in aMCI patients evaluated through adverse events, vital signs, clinical biochemistry, and physical and neurological examinations. Tertiary objectives are to analyze the effects of lenalidomide on brain amyloid loads (Florbetapir PET imaging) and neurodegeneration (volumetric MRI) by comparing pre- and post-dosing data. Finally, exploratory objectives will investigate whether blood inflammatory markers can serve as surrogate markers of therapeutic efficacy. Our study should determine whether lenalidomide is safe in AD subjects and whether it can alter the clinical progression of AD when administered before dementia onset. If effective, lenalidomide would become the first drug capable of delaying the trajectory of AD, which could lead the way to find additional, less toxic treatments in the near future.

4.
J Neurosurg ; 131(6): 1819-1828, 2018 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-30579269

RESUMO

OBJECTIVE: Effective treatments for recurrent, previously irradiated intracranial meningiomas are limited, and resection alone is not usually curative. Thus, the authors studied the combination of maximum safe resection and adjuvant radiation using permanent intracranial brachytherapy (R+BT) in patients with recurrent, previously irradiated aggressive meningiomas. METHODS: Patients with recurrent, previously irradiated meningiomas were treated between June 2013 and October 2016 in a prospective single-arm trial of R+BT. Cesium-131 (Cs-131) radiation sources were embedded in modular collagen carriers positioned in the operative bed on completion of resection. The Cox proportional hazards model with this treatment as a predictive term was used to model its effect on time to local tumor progression. RESULTS: Nineteen patients (median age 64.5 years, range 50-78 years) with 20 recurrent, previously irradiated tumors were treated. The WHO grade at R+BT was I in 4 (20%), II in 14 (70%), and III in 2 (10%) cases. The median number of prior same-site radiation courses and same-site surgeries were 1 (range 1-3) and 2 (range 1-4), respectively; the median preoperative tumor volume was 11.3 cm3 (range 0.9-92.0 cm3). The median radiation dose from BT was 63 Gy (range 54-80 Gy). At a median radiographic follow-up of 15.4 months (range 0.03-47.5 months), local failure (within 1.5 cm of the implant bed) occurred in 2 cases (10%). The median treatment-site time to progression after R+BT has not been reached; that after the most recent prior therapy was 18.3 months (range 3.9-321.9 months; HR 0.17, p = 0.02, log-rank test). The median overall survival after R+BT was 26 months, with 9 patient deaths (47% of patients). Treatment was well tolerated; 2 patients required surgery for complications, and 2 experienced radiation necrosis, which was managed medically. CONCLUSIONS: R+BT utilizing Cs-131 sources in modular carriers represents a potentially safe and effective treatment option for recurrent, previously irradiated aggressive meningiomas.


Assuntos
Materiais Biocompatíveis/administração & dosagem , Braquiterapia/métodos , Radioisótopos de Césio/administração & dosagem , Neoplasias Meníngeas/radioterapia , Meningioma/radioterapia , Recidiva Local de Neoplasia/radioterapia , Idoso , Colágeno/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Neoplasias Meníngeas/mortalidade , Neoplasias Meníngeas/cirurgia , Meningioma/mortalidade , Meningioma/cirurgia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Estudos Prospectivos , Taxa de Sobrevida/tendências , Resultado do Tratamento
5.
Artigo em Inglês | MEDLINE | ID: mdl-30322893

RESUMO

Chordoma is a rare, orphan cancer arising from embryonal precursors of bone. Surgery and radiotherapy (RT) provide excellent local control, often at the price of significant morbidity because of the structures involved and the need for relatively high doses of RT; however, recurrence remains high. Although our understanding of the genetic changes that occur in chordoma is evolving rapidly, this knowledge has yet to translate into treatments. We performed comprehensive DNA (paired tumor/normal whole-exome and shallow whole-genome) and RNA (tumor whole-transcriptome) next-generation sequencing analyses of archival sacral and clivus chordoma specimens. Incorporation of transcriptomic data enabled the identification of gene overexpression and expressed DNA alterations, thus providing additional support for potential therapeutic targets. In three patients, we identified alterations that may be amenable to off-label FDA-approved treatments for other tumor types. These alterations include FGFR1 overexpression (ponatinib, pazopanib) and copy-number duplication of CDK4 (palbociclib) and ERBB3 (gefitinib). In a third patient, germline DNA demonstrated predicted pathogenic changes in CHEK2 and ATM, which may have predisposed the patient to developing chordoma at a young age and may also be associated with potential sensitivity to PARP inhibitors because of homologous recombination repair deficiency. Last, in the fourth patient, a missense mutation in IGF1R was identified, suggesting potential activity for investigational anti-IGF1R strategies. Our findings demonstrate that chordoma patients present with aberrations in overlapping pathways. These results provide support for targeting the IGF1R/FGFR/EGFR and CDK4/6 pathways as treatment strategies for chordoma patients. This study underscores the value of comprehensive genomic and transcriptomic analysis in the development of rational, individualized treatment plans for chordoma.


Assuntos
Cordoma/genética , Cordoma/terapia , Perfilação da Expressão Gênica/métodos , Adulto , Idoso , Proteínas Mutadas de Ataxia Telangiectasia/genética , Quinase do Ponto de Checagem 2/genética , Quinase do Ponto de Checagem 2/metabolismo , Quinase 4 Dependente de Ciclina/genética , Proteínas de Ligação a DNA , Feminino , Gefitinibe , Genômica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Nucleares/genética , Piperazinas , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Inibidores de Proteínas Quinases , Piridinas , Receptor ErbB-3/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Neoplasias da Base do Crânio , Fatores de Transcrição/genética , Transcriptoma
6.
Front Neurol ; 8: 486, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28993751

RESUMO

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the degeneration of motor neurons. Though many molecular and genetic causes are thought to serve as predisposing or disease propagating factors, the underlying pathogenesis of the disease is not known. Recent discoveries have demonstrated the presence of inflammation propagating substrates in the central nervous system of patients afflicted with ALS. Over the past decade, this hypothesis has incited an effort to better understand the role of the immune system in ALS and has led to the trial of several potential immune-modulating therapies. Here, we briefly review advances in the role of such therapies. The clinical trials discussed here are currently ongoing or have been concluded at the time of writing.

7.
Front Neurol ; 8: 247, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28676785

RESUMO

We present the first quantitative analysis of atypical teratoid rhabdoid tumors (ATRT) in adults, including two patients from our own institutions. These are of interest as one occurred during pregnancy and one is a long-term survivor. Our review of pathological findings of 50 reported cases of adult ATRT leads us to propose a solely ectodermal origin for the tumor and that epithelial-mesenchymal transition (EMT) is a defining feature. Thus, the term ATRT may be misleading. Our review of clinical findings shows that ATRT tends to originate in mid-line structures adjacent to the CSF, leading to a high rate of leptomeningeal dissemination. Thus, we hypothesize that residual undifferentiated ectoderm in the circumventricular organs, particularly the pituitary and pineal glands, is the most common origin for these tumors. We note that if growth is not arrested soon after diagnosis, or after the first relapse/progression, death is almost universal. While typically rapidly fatal (as in our first case), long-term remission is possible (as in our second). Significant predictors of prognosis were the extent of resection and the use of chemotherapy. Glial differentiation (GFAP staining) was strongly associated with leptomeningeal metastases (chi-squared p = 0.02) and both predicted markedly worse outcomes. Clinical trials including adults are rare. ATRT is primarily a disease of infancy and radiotherapy is generally avoided in those aged less than 3 years old. Treatment options in adults differ from infants in that cranio-spinal irradiation is a viable adjunct to systemic chemotherapy in the adult population. Given the grave prognosis, this combined approach appears reasonable. As effective chemotherapy is likely to cause myelosuppression, we recommend that stem-cell rescue be available locally.

8.
Am J Case Rep ; 18: 700-706, 2017 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-28642454

RESUMO

BACKGROUND Sporadic inclusion body myositis (IBM) is the most common acquired myopathy seen in adults aged over 50 years, with a prevalence estimated at between 1 and 70 per million. Weakness of the diaphragm with loss of vital capacity is almost universal in IBM. This is almost always asymptomatic. When respiratory complications occur, they are most often due to aspiration. Respiratory failure due to diaphragmatic weakness is exceptionally rare, particularly as the presenting symptom of the disease. It is not currently considered to be a paraneoplastic syndrome. CASE REPORT Our patient presented with hypercarbic respiratory failure. This is the first such reported case without signs of weakness elsewhere of which we are aware. We suspected IBM based on her history of progressive weakness and findings on electromyography. There was a delay of 5 years in obtaining biopsy for confirmation, during which she presented with recurrent episodes of respiratory failure despite using non-invasive ventilation. An autopsy revealed the presence of papillary thyroid carcinoma with spread to local lymph nodes. On the basis that these co-morbidities are unlikely to have occurred by chance (we estimate 1×10-17), we hypothesize that IBM may be a paraneoplastic condition. We acknowledge that proof would require demonstrating a pathogenic antibody. CONCLUSIONS IBM should be considered in older patients (age >45) presenting with otherwise unexplained respiratory failure. A workup for possible malignancy in this setting appears reasonable.


Assuntos
Carcinoma Papilar/patologia , Metástase Linfática/patologia , Miosite de Corpos de Inclusão/diagnóstico , Síndromes Paraneoplásicas/diagnóstico , Insuficiência Respiratória/etiologia , Neoplasias da Glândula Tireoide/patologia , Autopsia , Feminino , Humanos , Pessoa de Meia-Idade , Câncer Papilífero da Tireoide
9.
Am J Case Rep ; 16: 893-8, 2015 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-26687433

RESUMO

BACKGROUND: Epidural anesthesia is the most commonly used method of pain relief during labor in the USA. It is not classically associated with alterations in level of alertness. Coma during the procedure is rare, with a reported incidence of 0.1-0.3%. CASE REPORT: An otherwise healthy patient experienced almost complete loss of brainstem function following routine epidural anesthesia during delivery. The episode lasted for less than 3 hours and the patient made a full recovery. To our knowledge, this is the most detailed clinical observation to date of this condition. CONCLUSIONS: Clinicians should be aware of this rare and potentially serious complication of epidural anesthesia. The case highlights the need for sensory input to maintain alertness through the activity of the ascending reticular activating system.


Assuntos
Anestesia Epidural/efeitos adversos , Anestésicos Locais/efeitos adversos , Tronco Encefálico/fisiopatologia , Coma/etiologia , Parto Obstétrico/efeitos adversos , Complicações na Gravidez , Sensação/fisiologia , Coma/diagnóstico , Feminino , Humanos , Gravidez , Adulto Jovem
10.
BMC Res Notes ; 8: 414, 2015 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-26341541

RESUMO

BACKGROUND: Glioblastoma is an aggressive and almost universally fatal tumor. The prognosis at the time of recurrence has generally been poor, with overall survival typically in the range of 4-40 weeks. The merits of surgical resection (vs. open biopsy, to confirm recurrence via histology) in addition to conventional adjuvant chemotherapy have been the subject of longstanding debate. We wondered whether it would possible to conduct a trial at our institution to settle this question definitively with Class I evidence. RESULTS: Initially, we had hoped to conduct a randomized, unblinded prospective clinical trial. However on closer inspection it appeared that such an undertaking would pose significant practical challenges. Thus we present our protocol in draft form. In keeping with recommended outcomes for these tumors, the primary endpoint would be median progression free survival. Secondary end points would be: median overall survival (mOS, from time of recurrence) and change in Karnofsky Performance Status over time. Patients would be eligible at the time of first recurrence if they had received conventional treatment until that point and at least 1 month had elapsed since the time of radiation. All patients would be considered potentially eligible for enrollment (unless the decision regarding resection was already clear-cut in view of other factors). Using Cox's proportional hazards model, we estimate that at least 456 patients would be necessary to demonstrate an increase in the hazard ratio to 1.3 for those undergoing biopsy alone. This magnitude of benefit is estimated based on a review of retrospective studies. DISCUSSION: If restricted to our Institution alone, which sees approximately 100-150 new cases of glioblastoma each year, a trial of this nature would be likely to take around 10 years. Furthermore, there may be significant reluctance on the part of patients and physicians to participate. There is also the opportunity cost of excluding patients from other trials to consider. We recognize that the estimate of the magnitude of effect may be conservative. As things stand, we feel that multi-institutional collaboration would almost certainly be required for an undertaking of this kind.


Assuntos
Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/terapia , Glioblastoma/cirurgia , Glioblastoma/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Projetos de Pesquisa , Adulto , Biópsia , Neoplasias Encefálicas/patologia , Quimiorradioterapia , Intervalo Livre de Doença , Glioblastoma/patologia , Humanos , Recidiva Local de Neoplasia , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Modelos de Riscos Proporcionais , Estudos Prospectivos , Reprodutibilidade dos Testes
12.
Oxf Med Case Reports ; 2015(2): 200-2, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25988079

RESUMO

Acute inflammatory demyelinating polyneuropathy or Guillain-Barré syndrome is well recognized as a presenting feature of human immunodeficiency virus (HIV) seroconversion and, to a lesser extent, as a complication of HIV infection, particularly immune reconstitution. Acute motor axonal neuropathy (AMAN) is much rarer in this setting. A case is presented of acute motor neuropathy, with features most consistent with AMAN in the setting of congenital HIV and prolonged non-compliance with antiretroviral treatment. The case throws new light on the pathogenesis of this condition. Macrophage activation is proposed as fundamental; the patient was predisposed by HIV as well as the use of granulocyte colony-stimulating factor and AMAN was then precipitated by a bacterial infection.

13.
Case Rep Neurol ; 7(1): 30-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25873887

RESUMO

We report a case of Langerhans cell histiocytosis in a 64-year-old male who presented with symptoms and signs of brain involvement, including seizures and hypopituitarism. The diagnosis was confirmed with a biopsy of a lytic skull lesion. The disease affecting the bone showed no sign of progression following a short course of cladribine. Signs of temporal lobe involvement led to an additional biopsy, which showed signs of nonspecific neurodegeneration and which triggered status epilepticus. Lesions noted in the brainstem were typical for the paraneoplastic inflammation reported in this condition. These lesions improved after treatment with cladribine. They remained stable while on treatment with intravenous immune globulin.

14.
Front Oncol ; 5: 12, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25688335

RESUMO

Immunotherapy seeks to improve the body's immune response to a tumor. Currently, the principal mechanisms employed are: (1) to improve an aspect of the immune response (e.g., T cell activation) and (2) to encourage the targeting of particular antigens. The latter is typically achieved by exposing the immune system to the antigen in question, in vivo, or in vitro followed by re-introduction of the primed cells to the body. The clinical relevance of these approaches has already been demonstrated for solid tumors such as melanoma and prostate cancer. The central nervous system was previously thought to be immune privileged. However, we know now that the immune system is highly active in the brain and interacts with brain tumors. Thus, harnessing and exploiting this interaction represents an important approach for treating malignant brain tumors. We present a summary of progress in this area, focusing particularly on immune-checkpoint inhibition, vaccines, and T cell engineering.

15.
Front Neurol ; 5: 220, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25404928

RESUMO

METHODS: Leptomeningeal metastases (LM) in the setting of glioma have often been thought to carry a particularly poor prognosis. We sought to better characterize this phenomenon through a review of patients with glioma seen in our institution over the preceding 10 years. We focus here on 34 cases with LM due to grade III or IV glioma. Over the period in question, we estimate a prevalence of almost 4% in those affected by grade IV tumors. RESULTS: Leptomeningeal spread was present at the time of initial diagnosis in 4 patients. Among the others, LM occurred at the time of first progression of disease in 17. The median time to development of LM (excluding those where it was present at initial diagnosis) was 16.4 months [95% confidence interval (CI) 8.2-43.9]. The median time to further progression of disease following LM was 4.9 months (95% CI 3.1-6.9). Twenty-five patients were known to have died at the time of writing. Thus, median overall survival (OS) was 10.2 months (95% CI 8.8-14.7) following LM. At the time of diagnosis of LM, some form of treatment (chemotherapy and/or radiation vs. no treatment) increased OS (median 11.7 vs. 3.3 months, p < 0.001 by log-rank test). Use of radiation therapy (vs. no radiation) also increased OS, although the effect was more modest (7.8 vs. 16.8 months, p = 0.07). Higher Karnofsky Performance Status (KPS) at the time of diagnosis of LM was associated with OS (p = 0.007, median OS for KPS ≥90 19 months vs. 7.8 for KPS <90). In a two-variable model incorporating the use any treatment (vs. none) and KPS, the latter tended to be a more significant predictor of survival (p = 0.22 vs. p = 0.06 by likelihood-ratio test). This was also true for radiation (vs. none) and KPS (p = 0.27 vs. p = 0.02). No significant benefit could be demonstrated for the use of chemotherapy considered alone, either systemic or intrathecal. It should be noted that 4 of 9 patients receiving intrathecal chemotherapy had a ventriculo-peritoneal shunt in place during these injections, which may have reduced its effectiveness. CONCLUSION: Overall, treatment appears to improve outcomes. We favor maximal treatment, as tolerated, particularly with a KPS of ≥70. Such treatment would typically include radiation to the maximum tolerated dose, concurrent, and adjuvant chemotherapy (preferably with an alkyating agent), in addition to intrathecal treatment.

16.
Med Hypotheses ; 80(2): 197-200, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23245909

RESUMO

Posterior reversible encephalopathy syndrome (PRES) has been associated with many conditions - particularly inflammatory, neoplastic and following organ failure. We submit that Chronic Obstructive Pulmonary Disease (COPD) is a significant predisposing factor for a number of these cases. Increased levels of circulating TNF-alpha, IL-1 and endothelin-1 (ET-1) are herein proposed as key mediators of this association. This theory builds on the central role of endothelial dysfunction in the pathogenesis of PRES. To our knowledge, no association of PRES and COPD has been made to date. We believe that it has practical implications: it suggests a lower threshold for MRI scans in certain patients. We suggest that the diagnosis of PRES should particularly be considered in ICU patients with typical signs (seizures, blindness, encephalopathy). Prompt recognition may lead to changes in management.


Assuntos
Síndrome da Leucoencefalopatia Posterior/diagnóstico , Síndrome da Leucoencefalopatia Posterior/etiologia , Síndrome da Leucoencefalopatia Posterior/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/complicações , Barreira Hematoencefálica/patologia , Endotelina-1/sangue , Humanos , Interleucina-1/sangue , Imageamento por Ressonância Magnética , Modelos Biológicos , Fator de Necrose Tumoral alfa/sangue
17.
Epilepsy Res Treat ; 2012: 273175, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22953060

RESUMO

Aim. To evaluate the utility of a seizure care pathway for seizure presentations to the emergency department (ED) in order to safely avoid unnecessary admission and to provide early diagnostic and therapeutic guidance and minimize length of stay in those admitted. Methods. 3 studies were conducted, 2 baseline audits and a 12-month intervention study and prospective data was collected over a 12-month period (Nov 2008-09). Results. Use of the Pathway resulted in a reduction in the number of epilepsy related admissions from 341 in 2004 to 276 in 2009 (P = 0.0006); a reduction in the median length of stay of those admittedfrom 4-5 days in the baseline audits to 2 days in the intervention study (P ≤ 0.001); an improvement in time to diagnostic investigations such as CT brain, MRI brain and Electroencephalography (P ≤ 0.001, P ≤ 0.048, P ≤ 0.001); a reduction in readmission rates from 45.1% to 8.9% (P ≤ 0.001); and an improvement in follow-up times from a median of 16 weeks to 5 weeks (P < 0.001). From a safety perspective there were no deaths in the early discharged group after 12 months follow-up. Conclusion. The burden of seizure related admissions through the ED can be improved in a safe and effective manner by the provision of a seizure care pathway.

18.
Neurologist ; 18(4): 204-5, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22735246

RESUMO

Oxcarbazepine, a metabolite of carbamazepine, is used as an antiepileptic, analgesic for neuropathic pain and in the treatment of affective disorders. It has been approved by the Food and Drug Administration for partial seizures in adults as both adjunctive and monotherapy, and as adjunctive therapy in children aged from 2 to 16 years (http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4254b_07_05_KP%20OxcarbazepineFDAlabel102005.pdf). We present a case of serotonin syndrome, which was precipitated by this medicine in a patient who had been predisposed by long-term treatment with sertraline, a selective serotonin reuptake inhibitor. This is the first reported fatality due to this drug interaction and only the second case of serotonin syndrome reported with oxcarbazepine. Physicians should consider this risk when prescribing the above combination.


Assuntos
Analgésicos/efeitos adversos , Carbamazepina/análogos & derivados , Interações Medicamentosas , Inibidores Seletivos de Recaptação de Serotonina/administração & dosagem , Síndrome da Serotonina/induzido quimicamente , Sertralina/administração & dosagem , Idoso de 80 Anos ou mais , Analgésicos/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Fibrilação Atrial/complicações , Broncodilatadores/administração & dosagem , Carbamazepina/administração & dosagem , Carbamazepina/efeitos adversos , Doença da Artéria Coronariana/complicações , Depressão/complicações , Depressão/tratamento farmacológico , Diabetes Mellitus , Neuropatias Diabéticas/complicações , Evolução Fatal , Humanos , Hipertensão/complicações , Hipoglicemiantes/administração & dosagem , Masculino , Neuralgia/tratamento farmacológico , Oxcarbazepina , Doença Pulmonar Obstrutiva Crônica/complicações
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