MRI Default Mode Network Connectivity is Associated with Functional Outcome After Cardiopulmonary Arrest

Background

We hypothesized that the degree of preserved functional connectivity within the DMN during the first week after cardiopulmonary arrest (CPA) would be associated with functional outcome at hospital discharge.

Methods

Initially comatose CPA survivors with indeterminate prognosis at 72 h were enrolled. Seventeen CPA subjects between 4 and 7 days after CPA and 17 matched controls were studied with task-free fMRI. Independent component analysis was performed to delineate the DMN. Connectivity strength in the DMN was compared between CPA subjects and controls, as well as between CPA subjects with good outcome (discharge Cerebral Performance Category or CPC 1–2) and those with bad outcome (CPC 3–5). The relationship between connectivity strength in the posterior cingulate cortex (PCC) and precuneus (PC) within the DMN with discharge CPC was evaluated using linear regression.

Results

Compared to controls, CPA subjects had significantly lower connectivity strength in subregions of the DMN, the PCC and PC (p < 0.0001). Furthermore, connectivity strength in the PCC and PC was greater in CPA subjects with good outcome (n = 8) than those with bad outcome (n = 9) (p < 0.003). Among CPA subjects, the connectivity strength in the PCC and PC showed strong linear correlations with the discharge CPC (p < 0.005).

Conclusions

Among initially comatose CPA survivors with indeterminate prognosis, task-free fMRI demonstrated graded disruption of DMN connectivity, especially in those with bad outcomes. If confirmed, connectivity strength in the PC/PCC may provide a clinically useful prognostic marker for functional recovery after CPA.     

Multiagent chemotherapy studied in a xenograft model of medulloblastoma/primitive neuroectodermal tumour: analysis of the VETOPEC regimen.

Brain tumours remain the most important challenge in the treatment of childhood cancer. The intraocular (io) xenograft model was used to study components and variations of the VETOPEC multiagent chemotherapy regimen in the medulloblastoma/primitive neuroectodermal tumour (MB/PNET) xenograft cell line JRMB-6. VETOPEC, a combination of vincristine (VCR), etoposide (VP-16) and escalated dose cyclophosphamide (CPA), has been shown to be highly active in clinical trials. A total of 190 xenografted tumours were treated with one of nine regimens: saline; single agent CPA, VP-16 (single dose [sd], five dosages daily [dx5] or continuous infusion, [ci]) or VCR; combinations of CPA (dx5)+VP-16 (dx5 or ci) or CPA (dx5)+VP-16 (ci)+VCR (sd). Results were calculated using both response (volume reduction >50%) and 'time to progression' (TtP). Effectiveness of CPA was confirmed. Single-agent VCR or VP-16 produced no response. No difference was documented in TtP with VCR, VP-16 (sd) or VP-16 (dx5) versus control, but a significant prolongation occurred when VP-16 was given by ci (p=0.001). With the 3-agent combination of CPA+VP-16 (ci)+VCR a significantly prolonged TtP was documented versus both single agent CPA (p=0.003) and the combination of CPA+VP-16 (dx5) (p=0.004). The results suggest improved efficacy of VP-16 when given as ci in both single-agent and combination settings. The addition of VP-16 (ci)+VCR to an already effective dosage of CPA further prolongs TtP. These data support and progress VETOPEC phase II clinical studies and suggest potential further benefits of prolonged exposure to VP-16 by ci.     

Cancer procoagulant A: a factor X activating procoagulant from malignant tissue.

A procoagulant substance from malignant tissue may play a role in fibrin deposition in malignant tumors and possibly in the vascular thrombosis observed in cancer patients. The objective of the present study was to determine how this procoagulant, cancer procoagulant A (CPA), initiates coagulation. Diisopropylfluorophosphate (DFP) inhibited the procoagulant activity of CPA but did not inhibit that of rabbit brain thromboplastin (RBT). Factor VII depleted bovine plasma was effectively clotted by CPA but not by RBT. These results indicate that CPA is not a tissue thromboplastin but instead suggest that it is a serine protease that does not require factor VII for its procoagulant activity. RBT and CPA promoted the coagulation of factor VIII deficient and normal plasma at a similar rate, suggesting that CPA does not act via the intrinsic pathway. CPA did not directly activate purified prothrombin. However, CPA directly activated factor X and this activation was inhibited by DFP. Thus it appears that malignant tissue produces a protease capable of initiating coagulation by activating factor X.     

Primary cerebellopontine angle craniopharyngioma in a patient with Gardner syndrome

Craniopharyngiomas usually involve the sella and suprasellar space. Ectopic craniopharyngiomas have rarely been reported at the cerebellopontine angle (CPA). We report a rare primary craniopharyngioma of the CPA without extension into the sellar region. The lesion was initially detected by MRI during investigation of multiple scalp fibromas. Multiple osteomas of the skull and face were detected 2 years later, and colonic adenomatous polyposis was detected 4 years later; typical features of Gardner syndrome. This is the third report of a primary CPA craniopharyngioma in a patient with Gardner syndrome.     

A rare presentation of intracranial cysticercosis involving the cerebellopontine angle

Intracranial cysticercosis involving the cerebellopontine angle (CPA) is rare. Here we report a patient with intracranial cysticercosis in the left CPA; the initial diagnosis of the lesion was epidermoid cyst or cystic glioma. The patient subsequently underwent total lesion removal through a left suboccipital approach; however, postoperative histopathological examination showed the tumor to be an intracranial cysticercosis. The patient’s symptoms improved dramatically after microsurgery and praziquantel administration. Rare infection caused by cysticercosis involving the CPA should be highlighted in the differential diagnosis of intracranial space-occupying lesions.     

Childhood physical abuse, aggression, and suicide attempts among criminal offenders

Childhood physical abuse (CPA) has numerous short and long-term negative effects. One of the most serious consequences of CPA is an increased risk for suicide attempts. Clarifying the mechanisms by which CPA increases risk for suicidal behavior may enhance preventive interventions. One potential mechanism is a tendency toward aggression. In a sample of 266 criminal offenders, ages 18-62, we examined the relationships among CPA, lifetime aggression, and suicide attempts and tested lifetime history of aggression as a mediator of the relationship between CPA and suicide attempts. Results indicated that CPA and aggression were associated with suicide attempts. Consistent with our hypothesis, lifetime aggression mediated the CPA and suicide attempts relationship. Findings suggest that aggression may be an important mediator of the relationship between CPA and suicide attempts among criminal offenders, and are consistent with the possibility that treating aggression may reduce risk for suicide attempts.     

Cerebellopontine angle lesions in children

Background Cerebellopontine angle (CPA) lesions are more commonly found in adults in which they account for 5–10% of all intracranial tumors. However, they are uncommon in children, with an incidence of only 1%. Materials and methods This is a review of the management of CPA lesions in children admitted to the Hospital Nacional de Pediatría “Profesor Doctor Juan P. Garrahan” (Argentine National Pediatrics Hospital “Professor Juan P. Garrahan”) between January 1988 and December 2003. Results The series included 30 children with 33 CPA lesions, 20 arising from the subarachnoid space of the CPA and 13 from the vicinity and growing mainly into the CPA. Twenty-seven tumors were located in the left CPA (82%) and six (12%), on the right. Ten of the 30 patients developed hydrocephalus, but only three of these required treatment. All patients underwent retrosigmoid suboccipital craniotomy and microsurgical resection. Gross total removal was achieved in 12 cases, subtotal in 18, and fenestration of the cyst wall in the three arachnoid cysts. Ten patients have no sequelae, ten have mild deficit, three have severe deficits, and seven have died. Conclusion The CPA is a rare location for lesions in children, with clear predominance on the left side. Benign lesions are more frequent. Even though schwannoma is the most frequently found lesion, the histology varies widely.     

Primary Rathke’s cleft cyst in the cerebellopontine angle associated with apoplexy

Rathke’s cleft cyst (RCC) is a congenital, benign, epithelial tumor and mainly occurs in sellar region and occasionally in suprasellar region; ectopic RCC is exceedingly rare. We report an uncommon RCC in cerebellopontine angle (CPA) associated with RCC apoplexy and investigated the possible hypothesis of its origin. A 12-year-old female student was admitted to hospital for 3-month history of vertigo, headache, nausea, and vomiting and aggravated for 1 week. Magnetic resonance imaging (MRI) revealed a space-occupying lesion with short T1 and long T2 signals in the left CPA and an intracystic floating nodule with hypointensity on T1- and T2-weighted imaging. The patient underwent the total tumor removal via the retrosigmoid approach with a good recovery. Primary RCC was confirmed by pathology. Follow-up MRI showed no recurrence 3.5 years after craniotomy. Primary RCC can occur in CPA and present special neuroimaging features associated with RCC apoplexy. We presumed that a mimicking mechanism of ectopic craniopharyngioma in CPA leads to the formation in the present case. Microsurgical resection is the optimal strategy for management. Further research and longer follow-up are helpful to better understanding the pathogenesis and development history of RCC in CPA.     

Pediatric primary pilocytic astrocytoma of the cerebellopontine angle: a case report

Introduction  We describe a rare case of pediatric pilocytic astrocytoma presented as a right cerebellopontine angle (CPA) mass, completely separated from the brain stem and arising from the proximal VIII nerve portion. Case report  A 12-year-old boy, with no evidence of neurofibromatosis type 2, presented with progressive hearing loss at the right ear and headache. An initial enhanced magnetic resonance examination suggested the diagnosis of schwannoma. The tumor was resected by a suboccipital retrosigmoid approach. Discussion  Our case seems to be the first report of a primary pediatric CPA pylocitic astrocytoma arising from the VIII nerve complex and presenting internal auditory canal enlargement. It represents the third reported case of a primary CPA pilocytic astrocytoma (the second pediatric case with the first arising from V nerve) and the eighth report of primary CPA glioma, overall. We discuss the clinical, neuroradiological, and intraoperative findings, and we review the different hypothesis about the origin of these rare tumors.     

Endoscopic examination of the cerebellar pontine angle

This anatomic study describes how to optimize the use of the endoscope in the cerebellar pontine angle (CPA) through a retrosigmoid approach. Unlike the microscope, that only permits visualization of structures directly ahead, the endoscope can see ‘around the corner’, also showing the structures down narrow. Nevertheless, to use the endoscope it is necessary to insert it into the CPA that is full of neurovascular structures which limit its movements. Thus, to avoid damages it is important to inspect this region accurately, by means of preferential trajectories to insert the endoscope. A retrosigmoid approach was performed in cadaver heads, and the CPA region was inspected employing 0°, 45° rigid endoscopes (4 mm in diameter). The neurovascular structures of the CPA have been visualized using three trajectories. The limits of view offered by each trajectory as well as the neurovascular structures together with the obstacles encountered on each route have been described. The systematic adoption of three different endoscope trajectories at the CPA level permits to view from different angulation the same structure as well as its relationships with the surrounding nerves and vessels. Considerable experience on cadavers should have already been obtained with the endoscope prior to any application in the operating room.     

Modelling constant potential amperometry for investigations of dopaminergic neurotransmission kinetics in vivo.

Constant potential amperometry (CPA) was used for in vivo recording of extracellular dopamine (DA) after electrical stimulation of the medial forebrain bundle (MFB) (4 pulses, 2 mA, 20 or 100 Hz) in the striatum of the rat brain. CPA signals were analysed in the absence and presence of the DA uptake inhibitor nomifensine with the help of a mathematical model which considered both the influence of DA diffusion after its stimulated release and the Michaelis-Menten kinetics of cellular DA uptake from the extracellular space. We found an excellent conformity of experimentally obtained CPA signals and calculated curves. Mathematical analysis revealed that CPA signals were strongly influenced by DA diffusion. The kinetic parameters calculated from CPA signals in this study were in agreement with experimental determinations of Vmax and Km of extracellular DA uptake in other studies and reflect the particular pharmacological properties of nomifensine. CPA is a useful and efficient method for in vivo estimation of individual changes of DA kinetic parameters by pharmacological treatment.     

Adenosine A1 receptor activation preferentially protects cultured cerebellar neurons versus astrocytes against hypoxia-induced death

Administration of adenosine A1 receptor agonists in vivo is neuroprotective in various stroke models. Experiments using either mixed cultures of neurons and astrocytes or brain slices, in which several cell types are present, have demonstrated that activation of A1 receptors also is protective against hypoxia and/or hypoglycemia in vitro. In this study, we have examined the effect of the A1 agonist cyclopentyladenosine (CPA) on cellular damage, measured by efflux of lactate dehydrogenase (LDH), in highly enriched primary cultures of either neurons or astrocytes exposed to different metabolic insults. CPA reduced neuronal LDH release induced by a combination of hypoxia and substrate deprivation (“simulated ischemia”; IC₅₀=28 nM) or by hypoxia alone (IC₅₀=170 nM). In contrast, CPA had no effect on neuronal damage induced by substrate deprivation alone, nor did it affect ischemic death to astrocytes. The neuroprotective effects of CPA during simulated ischemia and hypoxia were reversed by the A1 antagonist 1, 3-dipropyl-8-cyclopentylxanthine (DPCPX). These data demonstrate that activation of an adenosine A1 receptor on neurons, but not astrocytes, is protective against cellular damage or death induced specifically by hypoxia as opposed to other metabolic insults such as hypoglycemia.     

Pure endoscopic removal of epidermoid tumors of the cerebellopontine angle

Purpose

Epidermoid tumors located in the cerebellopontine angle (CPA) are challenging lesions because they tend to grow slowly in the subarachnoid cisterns around delicate neurovascular structures and often extend into surgical anatomic corners. The aim of this paper is to demonstrate the advantages and limitations of purely endoscopic removal of the CPA epidermoids.

Methods

Six patients harboring an epidermoid tumor located in the CPA were treated using an endoscope-controlled microsurgical technique. A retrosigmoid suboccipital approach was used in all patients. The cerebellomedullary cistern and the cisterna magna were opened to allow cerebrospinal fluid drainage and cerebellar drop, thus yielding a wide and straight working channel to the CPA. Then, the tumor and its capsule were removed by the modified microsurgical instruments.

Result

The symptoms caused by mass effect of the lesion resolved after surgery. There were no deaths, but permanent deficits occurred in one patient whose cranial nerves VII/VIII complex was accidentally lesioned. Tumors and their capsules were totally removed in five cases. All patients were discharged 3–5 days after surgery. To date, no recurrences have been observed (follow-up range 14–50 months).

Conclusion

The endoscope-controlled microsurgical technique enables a safe tumor removal even when parts of the lesion are not visible in a straight line in CPA epidermoids. By angled endoscopic lenses, tumor extending into adjacent cranial compartments or surgical anatomic corners can be removed through a single small craniotomy without retracting neurovascular structures.     

Ewing's Sarcoma/Peripheral Primitive Neuroectodermal Tumor in the Cerebellopontine Angle : Diagnosis and Treatment

Ewing''s sarcoma/primitive neuroectodermal tumor (ES/PNET) is an unusual malignancy with aggressive behavior. ES/PNET in the cerebellopontine angle (CPA) is extremely uncommon, and we report on a rare case here. A 31-year-old man presented with one month history of left facial palsy, hearing loss, swallowing difficulty, and hoarseness. Magnetic resonance images showed a large mass in the left CPA and a small one in the right cerebellar hemisphere. The patient underwent a surgery for the CPA mass lesion, and the pathology was compatible with ES/PNET. Radiation therapy and chemotherapy were administered. In contrast to the initial radiologic findings resembling vestibular schwannoma or meningioma, ES/PNET had several distinct clinical features. A patient with a CPA mass and presenting unusual clinical features should be suspected of having a rare malignancy.     

Radiological approach to basilar invagination type B: Reliability and accuracy

ObjectivesThis study aims to determine the reliability of the radiological tests used in the diagnosis of basilar invagination (BI).MethodsPatients diagnosed with type B basilar invagination, who had both magnetic resonance (MR) and computed tomography (CT) imaging between January 2014 and November 2019 were included in this retrospective reliability study. In this study, distance from odontoid apex to Chamberlain’s line (OA-CL) was accepted as a reference method for the diagnosis. Forty-two BI cases and 79 controls were included. Three radiologists with different levels of experience individually evaluated OA-CL, Boogard’s angle (BoA), clivo-axial angle (CXA), clivo-dens angle (CDA), and clivo-palate angle (CPA) on midsagittal CT and MR images. Statistical analysis was made with the intraclass correlation coefficient (ICC), t-test, and receiver operating characteristic (ROC) curve.ResultsThe ICC for CT and MR were; 0.977?0.973 (OA-CL), 0.912?0.882 (BoA), 0.845?0.846 (CXA), 0.862?0.864 (CDA), and 0.762?0.747 (CPA) respectively (P < 0.001). The areas under the ROC curve were 0.977 (BoA), 0.832 (CXA), 0.852 (CDA), and 0.719 (CPA) (P < 0.001). The cut-off measures were ≥137.84° (BoA), ≤149.25° (CXA), ≤129.58° (CDA), and ≤61.83° (CPA). The diagnostic accuracies were 0.954 (BoA), 0.664 (CXA), 0.704 (CDA), 0.438 (CPA) (P < 0.001).ConclusionsOA-CL and BoA express excellent inter-rater agreement than CXA, CDA, and CPA, which are limited due to morphological variations and head spatial position. BoA is the second most reliable diagnostic test. CXA, CDA, should only be used for complementary information. CPA was found inadequate for the diagnosis of BI.?     

桥小脑角区脑膜瘤的分型及显微外科治疗

目的 探讨桥小脑角区脑膜瘤的分型及显微外科治疗。方法 回顾性分析2008年6月至2017年3月收治的76例桥小脑角区脑膜瘤的临床资料，根据术前检查及术中判断分为内听孔前型31例，内听孔后型17例，大型联合型28例。73例采用枕下乙状窦后入路，2例使用颞下入路，1例使用翼点入路。结果 肿瘤全切除71例，次全切除5例。术后随访1~10年，术后新增神经症状15例，其余病人术后症状均改善；复查头颅MRI，复发3例；死亡2例。结论 显微手术切除桥小脑角区脑膜瘤可获得满意效果及良好预后；扩大枕下乙状窦后入路可满足绝大多数桥小脑角区脑膜瘤切除的需要；颅神经、岩静脉及重要动脉的保护和处理在桥小脑角区脑膜瘤显微外科治疗中具有重要意义。     

Activation of adenosine A1 receptors by drugs to lower plasma glucose in streptozotocin-induced diabetic rats

To examine the role of the adenosine A1 receptor in glucose regulation in the absence of insulin, the present study investigated the changes of plasma glucose in male streptozotocin-induced diabetic rats (STZ-diabetic rats) using dipyridamole to increase endogenous adenosine and N6-cyclopentyladenosine (CPA) to activate the adenosine A1 receptor. Intravenous injections of dipyridamole or CPA induced a dose-dependent decrease of plasma glucose in fasting STZ-diabetic rats. Plasma glucose lowering action of dipyridamole, like that of CPA, was inhibited in a dose-dependent manner by pre-treatment with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) or 8-(p-sulfophenyl)theophylline (8-SPT) at which block the adenosine A1 receptors. Action of the adenosine A1 receptors can thus be considered. In isolated skeletal muscle, CPA enhanced the glucose uptake in a concentration-dependent manner. Blockade of this action by DPCPX and 8-SPT again supported the mediation of the adenosine A1 receptor. Also, CPA produced an increase of glycogen synthesis in isolated soleus muscle. Moreover, CPA decreased plasma triglyceride and cholesterol levels significantly in STZ-diabetic rats. These results suggest that activation of adenosine A1 receptors can increase glucose utilization in peripheral tissues by increasing tissue uptake and glycogen synthesis to lower plasma glucose in rats lacking insulin.     

Afferent-inherent regulation of myosin heavy chain isoforms in rat muscle spindles

Whether afferents exert their morphogenetic influence on spindles through release of trophic factors at intrafusal fiber junctions or via participation in proprioceptive pathways which modulate the motor activity to muscles was investigated by comparing myosin heavy chain (MHC) expression in intrafusal fibers after ablation of afferents (deafferentation, or DA) to the extensor digitorum longus (EDL) of adult rats or after ablation of the corresponding central processes of afferents to the spinal cord (central-process ablation, or CPA). DA and CPA elicited an exaggerated pedal plantarflexion, and hypertrophy of the EDL concomitant with atrophy of the soleus in the affected hindlimb. Frequencies and patterns of expression of seven MHCs expressed by intrafusal fibers in CPA muscles were indistinguishable from normal rats. However, frequencies and patterns of expression of several MHCs were abnormal following DA. Thus factors transported anterogradely from afferents to intrafusal fibers may regulate MHC expression in intrafusal fibers. © 1997 John Wiley & Sons, Inc. Muscle Nerve 20: 1549–1560, 1997     

Metastatic lung cancer in the cerebellopontine angles mimicking bilateral acoustic neuroma.

Bilateral cerebellopontine angle (CPA) tumors identified on MRI are considered bilateral acoustic neuromas, the definitive diagnostic criterion of neurofibromatosis 2 (NF-2). We report the case of a 67-year-old man with progressive bilateral hearing loss, vertigo, and imbalance. MRI revealed bilateral enhancing CPA lesions, which were suggestive of acoustic neuromas and a diagnosis of NF-2. However, autopsy showed metastatic adenocarcinoma of the lung. Therefore, metastatic carcinoma to the CPA can mimic bilateral acoustic neuromas; imaging studies alone may be insufficient to diagnose NF-2.