Assuntos
Síndrome de Kluver-Bucy , Neurologia , Humanos , Estados Unidos , Neuropatologia , NeurocirurgiõesRESUMO
Background and Objective: Drug-resistant epilepsy (DRE), also known as medically refractory epilepsy, is a disorder of high prevalence and negatively impacts a patients quality of life, neurodevelopment, and life expectancy. Pediatric epilepsy surgery has been conducted since the late 1800s, and randomized controlled trials have demonstrated the marked effectiveness of surgery on seizure reduction and the potential for cure. Despite the strong evidence for pediatric epilepsy surgery, there is also strong evidence describing its underutilization. The objective of this narrative review is to describe the history, strength, and limitations in the evidence of surgery for pediatric drug resistant epilepsy. Methods: This narrative review was conducted utilizing standard search engines to include the relevant articles on the topic of surgery for drug resistant epilepsy in children, with main keywords including surgery in pediatric epilepsy and drug-refractory epilepsy. Key Content and Findings: The first components describe the historical perspective of pediatric epilepsy surgery and the evidence that highlight the strengths and limitations of epilepsy surgery. We then highlight the importance of presurgical referral and evaluation, followed by a section detailing the surgical options for children with DRE. Lastly, we provide a perspective on the future of pediatric epilepsy surgery. Conclusions: Evidence supports the role for surgery in pediatric medically refractory epilepsy in seizure frequency reduction, improved curative rates, and improvements in neurodevelopment and quality of life.
RESUMO
Background: The goals of operative treatment for unilateral coronal synostosis (UCS) are to improve appearance and allow unrestricted brain growth. However, for severe unilateral premature closure of the coronal suture, existing methods do not address the compression of the brain or expand the volume of the skull cavity. We report our retrospective experience with bilateral fronto-orbital advancement combined with cranial vault release using a free-floating bone flap (CVR + FFBF) technique and the resulting changes in the anterior cranial vault asymmetry index (ACVAI) and intracranial volume. Methods: Twenty patients with UCS who underwent bilateral fronto-orbital advancement combined with CVR + FFBF technique from April 2014 to May 2019 were included. Surgical efficacy was evaluated by the ACVAI and intracranial volume before the operation, 1 week after the operation, and at the last follow-up (average 19.8 months; range, 12 to 40 months). The measurement data are presented as the mean ± standard deviation and were statistically analyzed by t-test. Results: The ACVAI was 9.07%±3.55% before the operation, 3.56%±3.42% 1 week after the operation, and 3.13%±2.41% at the last follow-up. The ACVAI 1 week after the operation was significantly lower than that before the operation (t=4.827, P<0.001). There was no significant difference between the ACVAI 1 week after the operation and at the last follow-up (t=0.660, P=0.517). The intracranial volume was 1,027.85±112.25 mL in patients before the operation and 1,131.92±161.71 mL in the normal control group, which was a statistically significant difference (t=2.364, P=0.023). The intracranial volume significantly increased 1 week after surgery: 1,081.62±111.10 mL (t=8.703, P<0.001), and this trend continued at the last follow-up (1,386.90±119.30 mL) similarly to the normal control group (1,438.22±89.28 mL). At the last follow-up, there was no significant difference between the two groups (t=1.540, P=0.132). Conclusions: For the treatment of UCS, bilateral fronto-orbital advancement combined with CVR + FFBF technique offers functional and cosmetic outcomes in terms of intracranial volume expansion and fronto-orbital symmetry.
RESUMO
BACKGROUND: Iatrogenic vascular injury is an uncommon complication of anterior and/or posterior surgical approaches to the cervical spine. Although the results of this injury may be life-threatening, mortality/morbidity can be reduced by an understanding of its mechanism and proper management. METHODS: We conducted a literature review to provide an update of this devastating complication in spine surgery. A total of 72 articles including 194 cases of vascular lesions following cervical spine surgery between 1962 and 2021 were analyzed. RESULTS: There were 53 female and 41 male cases (in addition to 100 cases with unreported sex) with ages ranging from 3 to 86 years. The vascular injuries were classified according to the spinal procedures, such as anterior or posterior cervical spine surgery. The interval between the symptom of the vascular injury and the surgical procedure ranged from 0 to 10 years. Only two-thirds of patients underwent intra- or postoperative imaging and the most frequently injured vessel was the vertebral artery (86.60%). Laceration was the most common lesion (41.24%), followed by pseudoaneurysm (16.49%) and dissection (5.67%). Vascular repair was performed in 114 patients. The mortality rate was 7.22%, and 18.04% of patients had 1 or more other complications. Most presumed causes of vascular lesions were by instrumentation/screw placement (31.44%) or drilling (20.61%). Sixteen patients had an anomalous artery. Direct microsurgical repair was achieved in only 15 cases. CONCLUSIONS: Despite increased anatomical knowledge and advanced imaging techniques, we need to consider the risk of vascular injury as a surgical complication in patients with cervical spine pathologies.
Assuntos
Lesões do Sistema Vascular , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Parafusos Ósseos/efeitos adversos , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Criança , Pré-Escolar , Feminino , Humanos , Doença Iatrogênica/epidemiologia , Masculino , Pessoa de Meia-Idade , Lesões do Sistema Vascular/diagnóstico por imagem , Lesões do Sistema Vascular/etiologia , Artéria Vertebral/diagnóstico por imagem , Artéria Vertebral/lesões , Adulto JovemRESUMO
BACKGROUND: Brain abscesses are well-known to neurologic surgeons with well-recognized presentations, which include seizures, neurologic deficit, and headache. Rare symptoms may lead to a delay in diagnosis, which can be life threatening in the setting of a brain abscess. CASE DESCRIPTION: We present the case of a 46-year-old male with intractable hiccups found to have an abscess of the right basal ganglia. The brain abscess was treated by frameless stereotactic-guided aspiration. The patient's hiccups improved after surgical aspiration and medical management. CONCLUSIONS: A comprehensive literature review confirmed brain abscess as a rare cause of intractable hiccups. In addition, there are few reports of lesions of the basal ganglia causing intractable hiccups. Aspiration and medical therapy resulted in resolution of the hiccups. Knowledge of the hiccup reflex arc and unusual presentation of basal ganglia lesions may shorten time to diagnosis.
Assuntos
Gânglios da Base/cirurgia , Abscesso Encefálico/complicações , Infecções Bacterianas do Sistema Nervoso Central/complicações , Infecções por Haemophilus/complicações , Soluço/etiologia , Anti-Infecciosos/uso terapêutico , Gânglios da Base/diagnóstico por imagem , Abscesso Encefálico/diagnóstico por imagem , Abscesso Encefálico/tratamento farmacológico , Abscesso Encefálico/cirurgia , Ceftriaxona/uso terapêutico , Infecções Bacterianas do Sistema Nervoso Central/diagnóstico por imagem , Infecções Bacterianas do Sistema Nervoso Central/tratamento farmacológico , Infecções Bacterianas do Sistema Nervoso Central/cirurgia , Infecções por Haemophilus/diagnóstico por imagem , Infecções por Haemophilus/tratamento farmacológico , Infecções por Haemophilus/cirurgia , Haemophilus parainfluenzae/isolamento & purificação , Soluço/diagnóstico por imagem , Soluço/tratamento farmacológico , Soluço/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Metronidazol/uso terapêutico , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
A strategy to precisely engineer lipidoid-telodendrimer binary hybrid nanoparticles that offer enhanced cell membrane permeability for therapeutic proteins to reach the intracellular targets is established. The highly controllable biochemical and physical properties of the nanoparticles make them promising for protein-based brain cancer treatment with the assistance of convection-enhanced delivery.
Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Lipídeos/química , Nanopartículas/química , Proteínas/administração & dosagem , Proteínas/química , Animais , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Humanos , Modelos Teóricos , Proteínas/uso terapêuticoRESUMO
Novel nanocarriers are highly demanded for the delivery of heterogeneous protein therapeutics for disease treatments. Conventional nanoparticles for protein delivery are mostly based on the diffusion-limiting mechanisms, e.g., physical trapping and entanglement. We develop herein a novel linear-dendritic copolymer (named telodendrimer) nanocarrier for efficient protein delivery by affinitive coating. This affinity-controlled encapsulation strategy provides nanoformulations with a small particle size (<30 nm), superior loading capacity (>50% w/w) and maintained protein bioactivity. We integrate multivalent electrostatic and hydrophobic functionalities synergistically into the well-defined telodendrimer scaffold to fine-tune protein binding affinity and delivery properties. The ion strength and density of the charged groups as well as the structure of the hydrophobic segments are important and their combinations in telodendrimers are crucial for efficient protein encapsulation. We have conducted a series of studies to understand the mechanism and kinetic process of the protein loading and release, utilizing electrophoresis, isothermal titration calorimetry, Förster resonance energy transfer spectroscopy, bio-layer interferometry and computational methods. The optimized nanocarriers are able to deliver cell-impermeable therapeutic protein intracellularly to kill cancer cells efficiently. In vivo imaging studies revealed cargo proteins preferentially accumulate in subcutaneous tumors and retention of peptide therapeutics is improved in an orthotopic brain tumor, these properties are evidence of the improved pharmacokinetics and biodistributions of protein therapeutics delivered by telodendrimer nanoparticles. This study presents a bottom-up strategy to rationally design and fabricate versatile nanocarriers for encapsulation and delivery of proteins for numerous applications.
Assuntos
Dendrímeros/química , Nanocápsulas/química , Proteínas/administração & dosagem , Animais , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Camundongos Nus , Modelos Moleculares , Neoplasias/tratamento farmacológico , Proteínas/farmacocinética , Eletricidade EstáticaRESUMO
OBJECTIVE: Cranioplasty is one of the most common neurosurgical procedures, yet has one of the greatest rates of infection among cranial operations. Although studies have reported on cranioplasty complications, it is unclear what factors contribute to the high rate of infection. This study aims to determine which patient characteristics and operative factors lead to postcranioplasty infections. METHODS: This was a retrospective chart review of 186 patients. Factors analyzed included sex, reason for cranioplasty, type of infection, medical comorbidities, and surgical factors. RESULTS: The overall infection rate was 24%. Skin flora was the most common pathogen. Wound dehiscence and presence of a postoperative fluid collection were associated significantly with a greater rate of infection (P < 0.001), whereas the use of autologous bone flap and a state of immunosuppression trended toward statistical significance (P = 0.075 and P = 0.089, respectively). Male sex, history of previous infection, history of craniectomy for trauma, cranioplasty size, and time to cranioplasty were not found to be significant factors related to cranioplasty infection. CONCLUSIONS: Although wound dehiscence and postoperative fluid collections were associated significantly with infection in this study, the number in each sample size was small, and further studies with a larger number of patients in each subgroup is necessary to validate our findings.
Assuntos
Craniotomia/efeitos adversos , Procedimentos Neurocirúrgicos/efeitos adversos , Infecção da Ferida Cirúrgica/epidemiologia , Adulto , Lesões Encefálicas/complicações , Derivações do Líquido Cefalorraquidiano , Comorbidade , Feminino , Humanos , Terapia de Imunossupressão/efeitos adversos , Masculino , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Pele/microbiologia , Retalhos Cirúrgicos/efeitos adversos , Infecção da Ferida Cirúrgica/microbiologiaRESUMO
Brain metastasis is a common cause of mortality in patients with cancer, and is associated with poor prognosis. There is a current requirement for the identification of relevant brain metastasis tumor models, which may be used to test novel therapeutic agents and delivery systems in preclinical studies. The present study aimed to investigate the development of a murine model of brain metastasis, and the application of bioluminescence imaging (BLI) for monitoring tumor growth and response to targeted toxins (TT). A luciferasemodified human brain metastasis cell line was implanted into the caudateputamen of athymic mice using a stereotactic frame. Tumor growth was monitored by BLI, and tumor volume was calculated from threedimensional measurements of serial histopathological sections. Histopathological analyses revealed the presence of tumor growth within the caudateputamen of all of the mice, and BLI was shown to be correlated with tumor volume. To evaluate whether this model would allow the detection of a therapeutic response, mice bearing metastatic brain tumor cell xenografts were treated with TT delivered by convectionenhanced delivery (CED), via a microosmotic pump system. The TTtreated groups were submitted to metastatic brain tumor cell experiments, the results of which suggested that TT treatment delayed tumor growth, as determined by BLI monitoring, and significantly extended the survival of the mice. The results of the present study demonstrated the efficacy of a brain metastasis model for CED of TT via a microosmotic pump system in athymic mice, in which tumor growth and response to therapy were accurately monitored by BLI. In conclusion, this model may be wellsuited for preclinical testing of potential therapeutics for the treatment of patients with metastatic brain tumors.
Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/secundário , Convecção , Imunotoxinas/administração & dosagem , Bombas de Infusão , Medições Luminescentes/métodos , Animais , Modelos Animais de Doenças , Xenoenxertos , Humanos , Camundongos , Carga TumoralRESUMO
We present a 69-year-old woman who presented with chronic headaches and was found to have a pituitary mass on MRI, which was biopsied and said to be lymphocytic hypophysitis. The woman was placed on prednisone and followed with routine eye examinations. Two years later, the lesion gradually increased in size and the woman developed a decrease in peripheral vision in the right eye. An MRI showed abutment of the right optic nerve by the mass. A repeat endoscopic transsphenoidal biopsy/resection of the pituitary lesion was performed. Histopathological analysis of the specimen was consistent with diagnosis of xanthomatous hypophysitis (XH). XH is an inflammatory disorder of the pituitary gland characterized by an infiltration of lipid-laden histiocytes, also known as xanthoma cells. The mass was biopsied and a diagnosis of lymphocytic hypophysitis was made. The woman reported improved visual acuity and peripheral vision postoperatively. One year after the second resection, her visual symptoms worsened. Repeat MRI revealed expansion of the residual pituitary tissue. She was referred to the radiation oncology department for external beam radiation therapy and was placed on a maintenance dose of steroids. Since undergoing radiation therapy, her vision has improved slightly and her 3month MRI revealed stable lesion size. This woman illustrates a rare pituitary pathology presented with a literature review of published patients describing xanthomatous hypophysitis. A discussion of the clinical presentation, epidemiology, etiology, diagnosis, histology and treatment is provided.
Assuntos
Neuro-Hipófise/patologia , Neoplasias Hipofisárias/complicações , Xantomatose/complicações , Idoso , Anti-Inflamatórios/uso terapêutico , Biópsia , Feminino , Histiócitos/patologia , Humanos , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia , Procedimentos Neurocirúrgicos , Neuro-Hipófise/cirurgia , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Complicações Pós-Operatórias/terapia , Prednisona/uso terapêutico , Reoperação , Resultado do Tratamento , Transtornos da Visão/etiologia , Xantomatose/patologia , Xantomatose/cirurgiaRESUMO
Targeted toxins (TT) are molecules that bind cell surface antigens or receptors such as the transferrin or interleukin-13 receptor that are overexpressed in cancer. After internalization, the toxin component kills the cell. These recombinant proteins consist of an antibody or carrier ligand coupled to a modified plant or bacterial toxin such as diphtheria toxin (DT). These fusion proteins are very effective against brain cancer cells that are resistant to radiation therapy and chemotherapy. TT have shown an acceptable profile for toxicity and safety in animal studies and early clinical trials have demonstrated a therapeutic response. This review summarizes the characteristics of DT-based TT, the animal studies in malignant brain tumors and early clinical trial results. Obstacles to the successful treatment of brain tumors include poor penetration into tumor, the immune response to DT and cancer heterogeneity.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Toxina Diftérica/uso terapêutico , Imunotoxinas/uso terapêutico , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/química , Toxinas Bacterianas/efeitos adversos , Toxinas Bacterianas/química , Toxinas Bacterianas/uso terapêutico , Neoplasias Encefálicas/imunologia , Toxina Diftérica/efeitos adversos , Toxina Diftérica/química , Humanos , Imunotoxinas/administração & dosagem , Imunotoxinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes de Fusão/efeitos adversos , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/uso terapêutico , Transferrina/efeitos adversos , Transferrina/química , Transferrina/uso terapêuticoRESUMO
BACKGROUND: Staphylococcus lugdunensis is a coagulase-negative staphylococcus with aggressive and rapidly progressive infectious behavior. This organism has emerged as an important pathogen implicated in both community-acquired and nosocomial infections, including meningitis, brain abscess, catheter-related bacteremia, and ventriculoperitoneal shunt infection. CASE DESCRIPTION: We report the first known case of Staphylococcus lugdunensis intracranial abscess in a pediatric hydranencephalic patient, caused by a ventriculoperitoneal shunt-related infection. Further magnetic resonance imaging (MRI) confirmed a large abscess within the cranium that demonstrated multiple loculations. The patient received externalization of the right occipital ventricular catheter with evacuation of the brain abscess. Medical management included one week of intrathecal antibiotic treatment, and she was discharged on long-term intravenous rifampin and vancomycin, leading to cure of the infection. CONCLUSION: This case suggests that if Staphylococcus lugdunensis is identified, a virulent and prolonged clinical course with the production of destructive lesions, similar to those with S. aureus, should be expected. A course of antibiotic therapy and aggressive management that may include surgical treatment will be needed.
Assuntos
Abscesso Encefálico/tratamento farmacológico , Hidranencefalia/complicações , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus lugdunensis , Derivação Ventriculoperitoneal , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Abscesso Encefálico/etiologia , Abscesso Encefálico/cirurgia , Ceftriaxona/uso terapêutico , Pré-Escolar , Feminino , Humanos , Hidranencefalia/cirurgia , Injeções Espinhais , Procedimentos Neurocirúrgicos , Rifampina/uso terapêutico , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/cirurgia , Vancomicina/uso terapêuticoRESUMO
OBJECTIVE: To investigate the in vitro and in vivo anticancer efficacy of the immunotoxin DTATEGF against human NSCLC brain metastatic tumor PC9-BrM3 cell line. METHODS: The effect of the immunotoxin DTATEGF was tested for its ability to inhibit the proliferation of PC9-BrM3 cells in vitro by MTT assay. The cell cycle and the apoptosis of cells with 1 pmol/L DTATEGF were examined by flow cytometry. In vivo, 2 µg of DTATEGF or control Bickel3 was given intratumor to nude mice with established PC9-BrM3 xenografts on their hips, and tumor volumes were measured and tumor samples were investigated by immunchistochemistry SABC method. The microvessel density (MVD) was measured in each group. RESULTS: In vitro, DTATEGF killed PC9-BrM3 cells and showed an IC50 of 1 pmol/L. The apoptotic rate in the 1 pmol/L DTATEGF group was (64.0±0.5)% , significantly higher than that in the control group (1.5±0.4)% (P<0.01). The cell cycle was obviously inhibited by DTATEGF in a dose-dependent manner. The percentage of cells treated with 1 pmol/L DTATEGF in SubG0/G1 phase was (32.0±1.5)%, significantly higher than that in the control group (2.0±0.4)% (P<0.01). In vivo, DTATEGF significantly inhibited the growth of PC9-BrM3 hip tumors (P<0.05). The MVD of the DTATEGF group was (15.6±4.6)/mm2, significantly lower than that of the control group (31.2±5.4)/mm2 (P<0.01). CONCLUSION: DTATEGF inhibits the growth of the PC9-BrM3 cell line and induces its apoptosis. It is highly efficacious against human metastatic NSCLC brain tumor and against neovascularization.