RESUMO
Arteriovenous malformations (AVMs) of the ambient cistern are an extremely rare and complex subgroup of vascular malformation, representing a clinical challenge due to the deep-seated, highly eloquent anatomic location and the debilitating, life-threatening consequences related to hemorrhagic presentation and surgical morbidity. Ultimately, a tailored treatment, based on the presenting symptoms, AVM angioarchitecture, and annual risk of hemorrhage should be discussed among a multidisciplinary team to find the best individualized strategy balancing between the pros and cons of each approach. In Video 1, we present the case of a 60-year-old man with a hemorrhaged AVM of the right ambient cistern, present the pros and cons of each possible treatment strategy, and illustrate the successful resection of this lesion through a subtemporal-transtentorial microsurgical approach.
Assuntos
Fístula Arteriovenosa/cirurgia , Malformações Arteriovenosas Intracranianas/cirurgia , Microcirurgia/métodos , Procedimentos Neurocirúrgicos/métodos , Procedimentos Cirúrgicos Vasculares/métodos , Fístula Arteriovenosa/complicações , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/cirurgia , Cisterna Magna/patologia , Cisterna Magna/cirurgia , Humanos , Malformações Arteriovenosas Intracranianas/complicações , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND PURPOSE: Blood that enters the subarachnoid space (SAS) and its breakdown products are neurotoxic and are the principal inducers of brain injury after subarachnoid hemorrhage (SAH). Recently, meningeal lymphatic vessels (MLVs) have been proven to play an important role in clearing erythrocytes that arise from SAH, as well as other macromolecular solutes. However, evidence demonstrating the relationship between MLVs and brain injury after SAH is still limited. Therefore, we performed this study to observe the effects of meningeal lymphatic impairment on early brain injury (EBI) after experimental SAH. METHODS: The MLVs of C57BL/6 male adult mice were ablated by injecting Visudyne into the cisterna magna and transcranially photoconverting it with laser light. The MLVs were then examined by immunofluorescence staining for lyve-1. Next, both the MLV-ablated group and the control group (normal mice) underwent filament perforation to model SAH or sham operation. We assessed the cortical perfusion of all the mice before SAH induction, 5 min after SAH and 24 h after SAH. In addition, we evaluated neurological function deficits by Garcia scores and measured brain water content at 24 h post SAH. Then, neuroinflammation and neural apoptosis in the mouse brain were also examined. RESULTS: Visudyne and transcranial photoconversion treatment notably ablated mouse MLVs. Five minutes after SAH induction, cortical perfusion was significantly impaired, and after 24 h, this impairment was ameliorated considerably in the control group but ameliorated only slightly or worsened in the MLV-ablated group. Additionally, the MLVablated group presented worse neurological function deficits and more severe brain edema than the control group. More notably, neuroinflammation and neural apoptosis were also observed. CONCLUSION: Ablation of MLVs by Visudyne treatment exacerbated EBI after experimental SAH in mice. The worsening of EBI may have arisen from limited drainage of blood and other breakdown products, which are thought to cause brain edema, neuroinflammation, neuronal apoptosis and other pathological processes.
Assuntos
Lesões Encefálicas Traumáticas/patologia , Vasos Linfáticos/patologia , Meninges/patologia , Hemorragia Subaracnoídea Traumática/patologia , Animais , Apoptose , Água Corporal , Química Encefálica , Córtex Cerebral/irrigação sanguínea , Circulação Cerebrovascular , Cisterna Magna/patologia , Modelos Animais de Doenças , Encefalite/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Although the central canal is an integral component of the cerebral ventricular system, central canal dilation has not been examined adequately during the progression of subarachnoid hemorrhage-related hydrocephalus (SAH-H). Central canal dilation-associated ependymal cell desquamation or subependymal membrane rupture has been rarely reported. Herein, we try to describe possible mechanisms of central canal dilation "Hydromyelia," developing after SAH. A total of 25 New Zealand hybrid female rabbits were recruited. Five served as controls, and five received sham operations. In the remaining animals (n = 15), 0.5 mL/kg of autologous blood was injected into the cisterna magna twice on 0 and 2nd days. Five of these animals died within a few days. A total of 10 survivor animals decapitated 3 weeks later, and the brains and cervical spinal cords were histologically examined. Central canal volumes, ependymal cell numbers on the canal surfaces, and the Evans' indices of the ventricles were compared. On histological examination, central canal occlusion with desquamated ependymal cells and basement membrane rupture were evident. The mean Evans' index of the brain ventricles was 0.31, the mean central canal volume was 1.054 mm3, and the normal ependymal cell density was 4.210/mm2 in control animals; the respective values were 0.34, 1.287 mm3, and 3.602/mm2 for sham-operated animals, and 0.41, 1.776 mm3, and 2.923/mm2 in the study group. The differences were statistically significant (p < 0.05). Hydromyelia, an ignored complication of SAH-H, features ependymal cell desquamation, subependymal basement membrane destruction, blood cell accumulation on the subependymal cell basement membrane, and increased CSF pressure. Hydromyelia may be a significant complication following SAH.
Assuntos
Encéfalo/patologia , Modelos Animais de Doenças , Hidrocefalia/patologia , Medula Espinal/patologia , Hemorragia Subaracnóidea/patologia , Animais , Ventrículos Cerebrais/patologia , Cisterna Magna/patologia , Feminino , Hidrocefalia/etiologia , Hipertensão Intracraniana/etiologia , Hipertensão Intracraniana/patologia , Coelhos , Hemorragia Subaracnóidea/complicaçõesRESUMO
We present the case of a 42-year-old woman with a 5-week history of headache, progressive dysphagia, dysphonia, and hoarseness. A brain magnetic resonance imaging revealed an extra-axial cyst of the left lateral cerebellomedullary cistern. The subsequent histopathologic examination diagnosed a neuroenteric cyst. This case sheds light on the pivotal role of histologic identification of neuroenteric cyst, which could be crucial for further diagnostic investigations, especially in pediatric patients.
Assuntos
Doenças Cerebelares/diagnóstico por imagem , Doenças Cerebelares/cirurgia , Cisterna Magna/diagnóstico por imagem , Cisterna Magna/cirurgia , Defeitos do Tubo Neural/diagnóstico por imagem , Defeitos do Tubo Neural/cirurgia , Procedimentos Neurocirúrgicos/métodos , Adulto , Doenças Cerebelares/patologia , Cisterna Magna/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Defeitos do Tubo Neural/patologia , Paralisia/etiologia , Resultado do TratamentoRESUMO
BACKGROUND & AIMS: Hepatic encephalopathy (HE) is a serious neurologic complication in patients with liver cirrhosis. Very little is known about the role of the meningeal lymphatic system in HE. We tested our hypothesis that enhancement of meningeal lymphatic drainage could decrease neuroinflammation and ameliorate HE. METHODS: A 4-week bile duct ligation model was used to develop cirrhosis with HE in rats. Brain inflammation in patients with HE was evaluated by using archived GSE41919. The motor function of rats was assessed by the rotarod test. Adeno-associated virus 8-vascular endothelial growth factor C (AAV8-VEGF-C) was injected into the cisterna magna of HE rats 1 day after surgery to induce meningeal lymphangiogenesis. RESULTS: Cirrhotic rats with HE showed significantly increased microglia activation in the middle region of the cortex (P < .001) as well as increased neuroinflammation, as indicated by significant increases in interleukin 1ß, interferon γ, tumor necrosis factor α, and ionized calcium binding adaptor molecule 1 (Iba1) expression levels in at least 1 of the 3 regions of the cortex. Motor function was also impaired in rats with HE (P < .05). Human brains of patients with cirrhosis with HE also exhibited up-regulation of proinflammatory genes (NFKB1, IbA1, TNF-α, and IL1ß) (n = 6). AAV8-VEGF-C injection significantly increased meningeal lymphangiogenesis (P = .035) and tracer dye uptake in the anterior and middle regions of the cortex (P = .006 and .003, respectively), their corresponding meninges (P = .086 and .006, respectively), and the draining lymph nodes (P = .02). Furthermore, AAV8-VEGF-C decreased microglia activation (P < .001) and neuroinflammation and ameliorated motor dysfunction (P = .024). CONCLUSIONS: Promoting meningeal lymphatic drainage and enhancing waste clearance improves HE. Manipulation of meningeal lymphangiogenesis could be a new therapeutic strategy for the treatment of HE.
Assuntos
Sistema Glinfático/patologia , Encefalopatia Hepática/imunologia , Cirrose Hepática/complicações , Transtornos Motores/imunologia , Fator C de Crescimento do Endotélio Vascular/metabolismo , Animais , Linhagem Celular , Córtex Cerebral/imunologia , Córtex Cerebral/patologia , Cisterna Magna/imunologia , Cisterna Magna/patologia , Dependovirus/genética , Modelos Animais de Doenças , Vetores Genéticos/administração & dosagem , Vetores Genéticos/genética , Sistema Glinfático/imunologia , Encefalopatia Hepática/patologia , Humanos , Cirrose Hepática/imunologia , Linfangiogênese/imunologia , Masculino , Microglia/imunologia , Microglia/patologia , Transtornos Motores/patologia , Ratos , Fator C de Crescimento do Endotélio Vascular/genéticaRESUMO
BACKGROUND: We explored the clinical and molecular characteristics of molybdenum cofactor deficiency due to MOCS2 muations. METHODS: We summarize the genetic and clinical findings of previously reported patients with a MOCS2 mutation. We also present a new patient with novel neuroradiological findings associated with molybdenum cofactor deficiency due to a novel homozygous variant in the 5' untranslated region of the MOCS2 gene. RESULTS: The study population comprised 35 patients with a MOCS2 gene mutation. All reported children had delayed motor milestones. The major initial symptom was seizures in neonatal period. Facial dysmorphism was present in 61% of the patients. Only one patient had ectopia lentis. Agenesis of the corpus callosum and an associated interhemispheric cyst in our case are novel neuroradiological findings. CONCLUSIONS: The occurrence of neonatal seizures and feeding difficulties can be the first clinical signs of molybdenum cofactor deficiency. Although there is no effective therapy for this condition, early diagnosis and genetic analysis of these lethal disorders facilitate adequate genetic counseling.
Assuntos
Erros Inatos do Metabolismo dos Metais/genética , Sulfurtransferases/deficiência , Regiões 5' não Traduzidas/genética , Agenesia do Corpo Caloso/diagnóstico por imagem , Agenesia do Corpo Caloso/genética , Cisterna Magna/diagnóstico por imagem , Cisterna Magna/patologia , Bases de Dados Factuais , Encefalomalacia/diagnóstico por imagem , Encefalomalacia/genética , Face/anormalidades , Transtornos de Alimentação na Infância/genética , Feminino , Heterogeneidade Genética , Homozigoto , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Transtornos dos Movimentos/congênito , Transtornos dos Movimentos/genética , Neuroimagem , Fenótipo , Convulsões/congênito , Sulfurtransferases/genética , Substância Branca/diagnóstico por imagem , Substância Branca/patologiaRESUMO
Intradural spinal lipomas with intracranial extension are very rare and are typically diagnosed in childhood. Radical surgical excision usually causes a high rate of morbidity because of the firm adherence between the lipoma and neural tissues. In this report, we present a case of craniocervical intradural intramedullary lipoma in an adult patient. The patient underwent surgery with excision of the mass, leaving a sheet of lipoma on the tumor bed.
Assuntos
Neoplasias Infratentoriais/diagnóstico por imagem , Lipoma/diagnóstico por imagem , Neoplasias da Medula Espinal/diagnóstico por imagem , Adulto , Cisterna Magna/diagnóstico por imagem , Cisterna Magna/patologia , Descompressão Cirúrgica/métodos , Humanos , Neoplasias Infratentoriais/complicações , Neoplasias Infratentoriais/cirurgia , Lipoma/complicações , Lipoma/cirurgia , Imageamento por Ressonância Magnética , Masculino , Debilidade Muscular/etiologia , Neoplasia Residual , Parestesia/etiologia , Quadriplegia/etiologia , Reflexo Anormal , Neoplasias da Medula Espinal/complicações , Neoplasias da Medula Espinal/cirurgia , Tomografia Computadorizada por Raios XRESUMO
AIM: To investigate the relationship between neuron density of the superior cervical sympathetic ganglia and pupil diameter in subarachnoid hemorrhage. MATERIAL AND METHODS: This study was conducted on 22 rabbits; 5 for the baseline control group, 5 for the SHAM group and 12 for the study group. Pupil diameters were measured via sunlight and ocular tomography on day 1 as the control values. Pupil diameters were re-measured after injecting 0.5 cc saline to the SHAM group, and autologous arterial blood into the cisterna magna of the study group. After 3 weeks, the brain, superior cervical sympathetic ganglia and ciliary ganglia were extracted with peripheral tissues bilaterally and examined histopathologically. Pupil diameters were compared with neuron densities of the sympathetic ganglia and ciliary ganglia which were examined using stereological methods. RESULTS: Baseline values were; normal pupil diameter 7.180±620 ?m and mean neuron density of the superior cervical sympathetic ganglia 6.321±510/mm3, degenerated neuron density of ciliary ganglia was 5±2/mm3 after histopathological examination in the control group. These values were measured as 6.850±578 ?m, 5.950±340/mm3 and 123±39/mm3 in the SHAM group and 9.910±840 ?m, 7.950±764/mm3 and 650±98/mm3 in the study group. A linear relationship was determined between neuron density of the superior cervical sympathetic ganglia and pupil diameters (p < 0.005). Degenerated ciliary ganglia neuron density had an inverse effect on pupil diameters in all groups (p < 0.0001). CONCLUSION: Highly degenerated neuron density of the ciliary ganglion is not responsible for pupil dilatation owing to parasympathetic pupilloconstrictor palsy, but high neuron density of the pupillodilatatory superior cervical sympathetic ganglia should be considered an important factor for pupil dilatation.
Assuntos
Modelos Animais de Doenças , Midríase/patologia , Pupila/fisiologia , Hemorragia Subaracnóidea/patologia , Gânglio Cervical Superior/patologia , Animais , Cisterna Magna/patologia , Cisterna Magna/fisiopatologia , Gânglios Parassimpáticos/patologia , Gânglios Parassimpáticos/fisiopatologia , Masculino , Midríase/fisiopatologia , Degeneração Neural/patologia , Degeneração Neural/fisiopatologia , Neurônios/patologia , Neurônios/fisiologia , Coelhos , Hemorragia Subaracnóidea/fisiopatologia , Gânglio Cervical Superior/fisiopatologiaRESUMO
Meningiomas within the cisterna magna without dural attachment are extremely rare. To the best of our knowledge, only three cases of meningiomas within the cisterna magna have been reported in the literature. The authors present two cases of patient with the cisterna magna meningioma without dural attachment. (Case 1) A 36-year-old female presented with a 10-month history of numbness in the left hand. Magnetic resonance imaging (MRI) disclosed the presence of a contrast-enhanced tumor in the posterior fossa. A suboccipital craniectomy was performed, and the tumor located within the cisterna magna with no attachment to the dura. Diagnosis is made as clear cell meningioma. The postoperative course was uneventful, and a recurrence has not been observed for three years. (Case 2) A 58-year-old man presented with a well-circumscribed mass in the posterior fossa. At surgery, the tumor located within the cisterna magna with a connection to the right tenia. The tumor was totally removed without neurological deficits. At a 7-year follow-up, no evidence of a recurrence was observed. It is quite difficult to preoperatively diagnose as a cisterna magna meningioma without dural attachment. However, complete removal of the tumor should be achieved.
Assuntos
Cisterna Magna/diagnóstico por imagem , Dura-Máter/diagnóstico por imagem , Neoplasias Meníngeas/diagnóstico por imagem , Meningioma/diagnóstico por imagem , Adulto , Cisterna Magna/patologia , Cisterna Magna/cirurgia , Diagnóstico Diferencial , Dura-Máter/patologia , Dura-Máter/cirurgia , Feminino , Seguimentos , Humanos , Aumento da Imagem , Imageamento por Ressonância Magnética , Masculino , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/cirurgia , Meningioma/patologia , Meningioma/cirurgia , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To report radiological findings observed in computed tomography (CT) and magnetic resonance imaging (MRI) scans of the first cases of congenital infection and microcephaly presumably associated with the Zika virus in the current Brazilian epidemic. DESIGN: Retrospective study with a case series. SETTING: Association for Assistance of Disabled Children (AACD), Pernambuco state, Brazil. PARTICIPANTS: 23 children with a diagnosis of congenital infection presumably associated with the Zika virus during the Brazilian microcephaly epidemic. MAIN OUTCOME MEASURES: Types of abnormalities and the radiological pattern of lesions identified on CT and MRI brain scans. RESULTS: Six of the 23 children tested positive for IgM antibodies to Zika virus in cerebrospinal fluid. The other 17 children met the protocol criteria for congenital infection presumably associated with the Zika virus, even without being tested for IgM antibodies to the virus--the test was not yet available on a routine basis. Of the 23 children, 15 underwent CT, seven underwent both CT and MRI, and one underwent MRI. Of the 22 children who underwent CT, all had calcifications in the junction between cortical and subcortical white matter, 21 (95%) had malformations of cortical development, 20 (91%) had a decreased brain volume, 19 (86%) had ventriculomegaly, and 11 (50%) had hypoplasia of the cerebellum or brainstem. Of the eight children who underwent MRI, all had calcifications in the junction between cortical and subcortical white matter, malformations of cortical development occurring predominantly in the frontal lobes, and ventriculomegaly. Seven of the eight (88%) children had enlarged cisterna magna, seven (88%) delayed myelination, and six each (75%) a moderate to severe decrease in brain volume, simplified gyral pattern, and abnormalities of the corpus callosum (38% hypogenesis and 38% hypoplasia). Malformations were symmetrical in 75% of the cases. CONCLUSION: Severe cerebral damage was found on imaging in most of the children in this case series with congenital infection presumably associated with the Zika virus. The features most commonly found were brain calcifications in the junction between cortical and subcortical white matter associated with malformations of cortical development, often with a simplified gyral pattern and predominance of pachygyria or polymicrogyria in the frontal lobes. Additional findings were enlarged cisterna magna, abnormalities of corpus callosum (hypoplasia or hypogenesis), ventriculomegaly, delayed myelination, and hypoplasia of the cerebellum and the brainstem.
Assuntos
Agenesia do Corpo Caloso/diagnóstico , Encéfalo/patologia , Calcinose/diagnóstico , Hidrocefalia/diagnóstico , Malformações do Desenvolvimento Cortical/diagnóstico , Microcefalia/diagnóstico , Complicações Infecciosas na Gravidez , Infecção por Zika virus/diagnóstico , Adulto , Agenesia do Corpo Caloso/complicações , Encéfalo/diagnóstico por imagem , Brasil , Calcinose/complicações , Cisterna Magna/diagnóstico por imagem , Cisterna Magna/patologia , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Feminino , Humanos , Hidrocefalia/complicações , Imunoglobulina M/líquido cefalorraquidiano , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Malformações do Desenvolvimento Cortical/complicações , Microcefalia/complicações , Fibras Nervosas Mielinizadas/diagnóstico por imagem , Fibras Nervosas Mielinizadas/patologia , Tamanho do Órgão , Gravidez , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Adulto Jovem , Zika virus/imunologia , Infecção por Zika virus/complicações , Infecção por Zika virus/congênitoRESUMO
PURPOSE: The goal of this study was to identify direct cerebrospinal fluid (CSF) pathways in the interface between ventricles and cisterns. Such routes are hypothesized to be involved in alternative CSF flows in abnormal circumstances of CSF circulation. METHODS: Chronic obstructive hydrocephalus models were induced in ten Sprague-Dawley rats with kaolin injection into the cisterna magna. Three weeks after the kaolin injection, when thick arachnoid fibrosis obliterated the fourth ventricular outlets, cationized ferritin was stereotactically infused as a tracer into the lateral ventricle in order to observe the pathways from the ventricles to the subarachnoid space. Animals were killed in 48 h and brains were sectioned. CSF flow pathways were traced by the staining of ferritin with ferrocyanide. RESULTS: Eight out of ten rats developed hydrocephalus. The subarachnoid membranes of the convexity and basal cisterns were severely adhered such that most of the ferritin remained in the ventricles whereas basal and convexity cisterns were clear of ferritin. In six out of the eight hydrocephalus rats, ferritin leaked from the third ventricle into the quadrigeminal cistern, and from the lateral ventricle into the ambient cistern. CONCLUSIONS: The interfaces between the third ventricle and the quadrigeminal cistern, and between the lateral ventricle and the ambient cistern appear to be alternative CSF pathways in a pathologic condition such as obstructive hydrocephalus.
Assuntos
Líquido Cefalorraquidiano , Cisterna Magna/fisiopatologia , Hidrocefalia/patologia , Terceiro Ventrículo/fisiopatologia , Animais , Antidiarreicos/toxicidade , Cisterna Magna/patologia , Modelos Animais de Doenças , Ferritinas/metabolismo , Hidrocefalia/induzido quimicamente , Caulim/toxicidade , Masculino , Ratos , Ratos Sprague-Dawley , Terceiro Ventrículo/patologiaRESUMO
OBJECTIVE: We aimed to evaluate the relationship between aneurysm morphology, thalamoperforators' ischemia, outcome, and oculomotor nerve palsy (ONP) that continued during the follow-up period in 23 patients with complex unruptured basilar apex aneurysms (BAAs) treated with clipping. METHODS: Aneurysm morphology included the size, distance of neck from the posterior clinoid process, dome projection, and localization in the interpeduncular cistern (LIC). BAAs with neck >4 mm, posterior projection, retro/subsellar, and dome-to-neck ratios <1.2 were considered as complex. The poor outcome was defined as modified Rankin Scale (mRS) 2-6 at the 12 months' follow-up examination. RESULTS: All patients were treated by anterior temporal approach. Size (P < 0.0001) and LIC (P < 0.0001) were related to thalamoperforators' ischemia (n = 3, 13%). Size (P = 0.0010), dividing-posterior communicating artery (P = 0.0050), thalamoperforator's ischemia (P = 0.034), and LIC (P < 0.0001) were related to poor outcome (mRS 2: n = 3, 13%). The mean follow-up period was 368 ± 52 days. No patients developed a bleed and showed evidence of any residual or recurrent aneurysm during follow-up. Postoperative ONP occurred in 15 patients (65%) and all were partial. During follow-up, full recovery of the ONP was seen in 13 patients (57%), and it continued in 2 (8.7%). Size (P = 0.010) and posterior projection (P = 0.043) and LIC (P = 0.0050) were related to continued ONP. CONCLUSIONS: The present study suggested that unruptured BAA patients with LIC should be meticulously treated in case of performing clipping because it was related to thalamoperforators' ischemia, poor outcome, and continued ONP.
Assuntos
Isquemia Encefálica/epidemiologia , Cisterna Magna/patologia , Aneurisma Intracraniano/diagnóstico , Aneurisma Intracraniano/cirurgia , Doenças do Nervo Oculomotor/epidemiologia , Complicações Pós-Operatórias , Idoso , Feminino , Seguimentos , Humanos , Aneurisma Intracraniano/complicações , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do TratamentoRESUMO
Niemann-Pick type C1 (NPC) disease is a lysosomal storage disease caused by mutations in the NPC1 gene, leading to an increase in unesterified cholesterol and several sphingolipids, and resulting in hepatic disease and progressive neurological disease. We show that subcutaneous administration of the pharmaceutical excipient 2-hydroxypropyl-ß-cyclodextrin (HPßCD) to cats with NPC disease ameliorated hepatic disease, but doses sufficient to reduce neurological disease resulted in pulmonary toxicity. However, direct administration of HPßCD into the cisterna magna of presymptomatic cats with NPC disease prevented the onset of cerebellar dysfunction for greater than a year and resulted in a reduction in Purkinje cell loss and near-normal concentrations of cholesterol and sphingolipids. Moreover, administration of intracisternal HPßCD to NPC cats with ongoing cerebellar dysfunction slowed disease progression, increased survival time, and decreased the accumulation of brain gangliosides. An increase in hearing threshold was identified as a potential adverse effect. These studies in a feline animal model have provided critical data on efficacy and safety of drug administration directly into the central nervous system that will be important for advancing HPßCD into clinical trials.
Assuntos
Cisterna Magna/patologia , Cisterna Magna/fisiopatologia , Doença de Niemann-Pick Tipo C/tratamento farmacológico , Doença de Niemann-Pick Tipo C/fisiopatologia , Células de Purkinje/patologia , beta-Ciclodextrinas/uso terapêutico , 2-Hidroxipropil-beta-Ciclodextrina , Envelhecimento/patologia , Alanina Transaminase/sangue , Animais , Ataxia/sangue , Ataxia/complicações , Ataxia/patologia , Limiar Auditivo , Calbindinas/metabolismo , Gatos , Morte Celular , Imunofluorescência , Gangliosídeo G(M2)/metabolismo , Inflamação/complicações , Inflamação/patologia , Injeções Subcutâneas , Fígado/patologia , Hepatopatias/sangue , Hepatopatias/complicações , Hepatopatias/patologia , Pulmão/patologia , Doença de Niemann-Pick Tipo C/sangue , Doença de Niemann-Pick Tipo C/complicações , Células de Purkinje/metabolismo , Coloração e Rotulagem , Análise de Sobrevida , beta-Ciclodextrinas/administração & dosagemRESUMO
Potassium homeostasis is fundamental for the physiological functioning of the brain. Increased [K(+)] in the extracellular fluid has a major impact on neuronal physiology and can lead to ictal events. Compromised regulation of extracellular [K(+)] is involved in generation of seizures in animal models and potentially also in humans. For this reason, the investigation of K(+) spatio-temporal dynamics is of fundamental importance for neuroscientists in the field of epilepsy and other related pathologies. To date, the majority of studies investigating changes in extracellular K(+) have been conducted using a micropipette filled with a K(+) sensitive solution. However, this approach presents a major limitation: the area of the measurement is circumscribed to the tip of the pipette and it is not possible to know the spatiotemporal distribution or origin of the focally measured K(+) signal. Here we propose a novel approach, based on wide field fluorescence, to measure extracellular K(+) dynamics in neural tissue. Recording the local field potential from the somatosensory cortex of the mouse, we compared responses obtained from a K(+)-sensitive microelectrode to the spatiotemporal increases in fluorescence of the fluorophore, Asante Potassium Green-2, in physiological conditions and during 4-AP induced ictal activity. We conclude that wide field imaging is a valuable and versatile tool to measure K(+) dynamics over a large area of the cerebral cortex and is capable of capturing fast dynamics such as during ictal events. Moreover, the present technique is potentially adaptable to address questions regarding spatiotemporal dynamics of other ionic species.
Assuntos
Química Encefálica/fisiologia , Neuroimagem/métodos , Potássio/metabolismo , 4-Aminopiridina , Animais , Córtex Cerebral/patologia , Cisterna Magna/patologia , Convulsivantes , Estimulação Elétrica , Eletrodos , Fenômenos Eletrofisiológicos , Líquido Extracelular/metabolismo , Fluorescência , Corantes Fluorescentes , Camundongos , Convulsões/induzido quimicamente , Convulsões/patologiaRESUMO
The architecture of the spinal cord makes efficient delivery of recombinant adeno-associated virus (rAAV) vectors throughout the neuraxis challenging. We describe a paradigm in which small amounts of virus delivered intraspinally to newborn mice result in robust rAAV-mediated transgene expression in the spinal cord. We compared the efficacy of rAAV2/1, 2/5, 2/8, and 2/9 encoding EGFP delivered to the hindlimb muscle (IM), cisterna magna (ICM), or lumbar spinal cord (IS) of neonatal pups. IS injection of all four capsids resulted in robust transduction of the spinal cord with rAAV2/5, 2/8, and 2/9 vectors appearing to be transported to brain. ICM injection resulted in widespread expression of EGFP in the brain, and upper spinal cord. IM injection resulted in robust muscle expression, with only rAAV2/8 and 2/9 transducing spinal motor and sensory neurons. As proof of concept, we use the IS paradigm to express murine Interleukin (IL)-10 in the spinal cord of the SOD1-G93A transgenic mouse model of amyotrophic lateral sclerosis. We show that expression of IL-10 in the spinal axis of SOD1-G93A mice altered the immune milieu and significantly prolonged survival. These data establish an efficient paradigm for somatic transgene delivery of therapeutic biologics to the spinal cord of mice.
Assuntos
Esclerose Lateral Amiotrófica/terapia , Encéfalo/metabolismo , Dependovirus/genética , Terapia Genética/métodos , Medula Espinal/metabolismo , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/patologia , Animais , Animais Recém-Nascidos , Encéfalo/patologia , Capsídeo/metabolismo , Cisterna Magna/metabolismo , Cisterna Magna/patologia , Dependovirus/metabolismo , Expressão Gênica , Genes Reporter , Vetores Genéticos , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Humanos , Injeções Espinhais , Interleucina-10/genética , Interleucina-10/metabolismo , Camundongos , Camundongos Transgênicos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Medula Espinal/patologia , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Transdução GenéticaRESUMO
A 67-year-old woman was admitted for headache. The initial MRI showed a gadolinium-enhanced lesion in the prepontine area. Initial and repeated CSF examinations were negative for the fungal infection. Since the enhanced lesion expanded in the cisterns, and showed tumor-like appearance, brain biopsy was performed at 3 months from her first admission. Histological studies revealed filamentous fungal infection probably caused by the pseudallescheria boydii. Intrathecal miconazole injection through the Ommaya reservoir successfully ameliorated patient's symptoms and the MRI findings. Primary cisternal fungal infection showing tumor-like expansion typically fails to demonstrate its supportive findings by the CSF examination. Therefore, histopathological assessment after brain biopsy should be considered in cases that are not conclusive by means of conventional laboratory examinations.
Assuntos
Cisterna Magna/microbiologia , Cisterna Magna/patologia , Encefalite/microbiologia , Encefalite/patologia , Micoses , Idoso , Antifúngicos/administração & dosagem , Diagnóstico Diferencial , Encefalite/diagnóstico , Encefalite/tratamento farmacológico , Feminino , Humanos , Infusão Espinal , Imageamento por Ressonância Magnética , Miconazol/administração & dosagem , Prednisolona/administração & dosagem , Pseudallescheria/isolamento & purificação , Resultado do Tratamento , Voriconazol/administração & dosagemRESUMO
INTRODUCTION: Vasospasm is the most common cause of complication after a subarachnoid hemorrhage and tremendous efforts have been made to prevent it. A subarachnoid clot is the cause of the vasospasm and dissolving and washing it out is considered to be the best practice. Cisternal irrigation with urokinase and ascorbic acid has been widely used due to its proven effect. CASE PRESENTATION: A 60-year-old Japanese male presented with a severe headache was diagnosed with a subarachnoid hemorrhage and an immediate surgical obliteration was successfully performed. After clipping the aneurysm, a cisternal drainage tube was placed in the chiasmatic cistern. In order to clear the thick subarachnoid hemorrhage, a cisternal irrigation was performed. However, his consciousness deteriorated and his left pupil became dilated on the next day. A T1 sagittal magnetic resonance imaging scan showed an evidence of marked brain sagging with mild tonsillar descent. We continued intensive hydration and head-down positioning and the brain sagging was shown to have improved in the follow-up magnetic resonance imaging scan. CONCLUSIONS: We present a case in which our patient experienced brain sagging after a cisternal irrigation of a subarachnoid hemorrhage. A subdural hematoma and low intracranial pressure suggested intracranial hypotension. Sagittal magnetic resonance imaging images are useful to evaluate brain sagging and are shown sequentially here in our case report.
Assuntos
Cisterna Magna/patologia , Hipotensão Intracraniana/etiologia , Hemorragia Subaracnóidea/complicações , Irrigação Terapêutica/efeitos adversos , Vasoespasmo Intracraniano/etiologia , Hidratação/métodos , Humanos , Hipotensão Intracraniana/terapia , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Posicionamento do Paciente/métodos , Postura , Hemorragia Subaracnóidea/cirurgia , Resultado do Tratamento , Vasoespasmo Intracraniano/terapiaRESUMO
BACKGROUND: Kernicterus still occurs around the world; however, the mechanism of bilirubin neurotoxicity remains unclear, and effective treatment strategies are lacking. To solve these problems, several kernicterus (or acute bilirubin encephalopathy) animal models have been established, but these models are difficult and expensive. Therefore, the present study was performed to establish a novel kernicterus model that is simple and affordable by injecting unconjugated bilirubin solution into the cisterna magna (CM) of ordinary newborn Sprague-Dawley (SD) rats. METHODS: On postnatal day 5, SD rat pups were randomly divided into bilirubin and control groups. Then, either bilirubin solution or ddH2O (pHâ=â8.5) was injected into the CM at 10 µg/g (bodyweight). For model characterization, neurobehavioral outcomes were observed, mortality was calculated, and bodyweight was recorded after bilirubin injection and weaning. Apoptosis in the hippocampus was detected by H&E staining, TUNEL, flow cytometry and Western blotting. When the rats were 28 days old, learning and memory ability were evaluated using the Morris water maze test. RESULTS: The bilirubin-treated rats showed apparently abnormal neurological manifestations, such as clenched fists, opisthotonos and torsion spasms. Bodyweight gain in the bilirubin-treated rats was significantly lower than that in the controls (P<0.001). The early and late mortality of the bilirubin-treated rats were both dramatically higher than those of the controls (Pâ=â0.004 and 0.017, respectively). Apoptosis and necrosis in the hippocampal nerve cells in the bilirubin-treated rats were observed. The bilirubin-treated rats performed worse than the controls on the Morris water maze test. CONCLUSION: By injecting bilirubin into the CM, we successfully created a new kernicterus model using ordinary SD rats; the model mimics both the acute clinical manifestations and the chronic sequelae. In particular, CM injection is easy to perform; thus, more stable models for follow-up study are available.
Assuntos
Antioxidantes/efeitos adversos , Bilirrubina/efeitos adversos , Cisterna Magna , Modelos Animais de Doenças , Kernicterus , Animais , Animais Recém-Nascidos , Antioxidantes/farmacologia , Bilirrubina/farmacologia , Cisterna Magna/metabolismo , Cisterna Magna/patologia , Kernicterus/induzido quimicamente , Kernicterus/metabolismo , Kernicterus/patologia , Ratos , Ratos Sprague-DawleyRESUMO
The Dandy-Walker variant is a milder form of the Dandy-Walker complex and is characterized by normal-sized posterior fossa, mild vermian hypoplasia, and a cystic lesion that communicates with the fourth ventricle. This syndrome has been described in association with schizophrenia, obsessive-compulsive disorder, manic episode, psychosis (delusional type), and recurrent catatonia. The authors present two cases of mega cisterna magna associated with mania and catatonic schizophrenia.