Adjuvant Treatment in the Management of Low-Grade Gliomas

The use of chemotherapy in low-grade gliomas has been very thoroughly studied in the setting of oligodendrogliomas and oligoastrocytomas. According to the Radiation Oncology staff here at Thomas Jefferson University Hospital, the current practices in our institution are as follows: Three-dimensional conformal radiation is provided in patients with low-grade gliomas 2-4 weeks post-operatively. The total dose ranges between 50 and 54 Gy and is delivered in 1.8 fractions at five fractions per week. In the presence of recurrence, a stereotactic boost with or without re-operation is provided. For the most part, these practices are similar to the aforementioned recommendations. However, factors such as the age of the patient, and optimal timing of the radiation are not considered in our institution at this given time. Chemotherapy is restricted to patients with known pathology of oligodendroglioma. PCV is the chemotherapeutic agent of choice in both research recommendations and our clinical practice. Specifically, the use of PCV in an established oligodendroglioma case has shown to increase the time to progression and provide a statistically significant survival benefit. Furthermore, this response is augmented in patients with chromosomal analysis positive for the 1p and 19q allele mutation. For these patients, further chromosomal analysis is performed in order to predict the chemotherapy response rate. Recurrent disease is managed on a patient specific basis

Cerebrospinal Fluid Leakage and Cerebral Venous Sinus Thrombosis: A Case Report

Cerebrovascular venous thrombosis is an uncommon entity that may occur in the sinuses of the dura, the cortical veins, or the deep venous system. Common etiologies include states of hypercoagulability, such as oral contraceptives intake, malignancy, and trauma. Additional causes include inherent thrombophilic states, such as those caused by systemic lupus erythematosus, protein C or S deficiency, and antithrombin III deficiency. The pathogenesis of cerebral venous sinus thrombosis stems from the obstruction of venous outflow. Consequently, venous engorgement occurs, leading to decreased effective blood flow and white matter edema. Infarction or hemorrhage are not uncommon in the setting of venous thrombosis. Intracranial pressure also rises. The most common presenting symptom is headache.2,3 The impact of intracranial hypotension due to cerebrospinal fluid (CSF) leak on venous flow and thrombosis is not clear.1, 4-8, 10, 11 We present the case and treatment course of a patient who initially presented with an acute venous sinus thrombosis and in was later found to have a CSF leak and intracranial hypotension

Dural Arteriovenous Malformations: A Review of the Literature and a Presentation of the JHN Series

Dural arteriovenous malformations (DAVMs), also known as dural arteriovenous fistulas, are arteriovenous shunts from a dural arterial supply to a dural venous channel, typically supplied by pachymeningeal arteries and located near a major venous sinus.1 The etiology of these lesions is not fully understood. DAVMs in the pediatric population are associated with structural venous abnormalities ,2 but the majority of DAVMs are thought to be acquired. Different etiologies have been implicated in this phenomenon, namely: sinus thrombosis, trauma or surgery.2–

Flow-diversion panacea or poison?

Endovascular therapy is now the treatment of choice for intracranial aneurysms (IAs) for its efficacy and safety profile. The use of flow diversion (FD) has recently expanded to cover many types of IAs in various locations. Some institutions even attempt FD as first line treatment for unruptured IAs. The most widely used devices are the pipeline embolization device (PED), the SILK flow diverter (SFD), the flow redirection endoluminal device (FRED), and Surpass. Many questions were raised regarding the long-term complications, the optimal regimen of dual antiplatelet therapy, and the durability of treatment effect. We reviewed the literature to address these questions as well as other concerns on FD when treating IAs

Stereotactic Radiosurgery for Management of Cavernous Malformations

Cavernous malformations (CMs) are abnormal vascular formations of the brain with an estimated incidence of 0.4%-0.8% in the general population.1 CMs have the potential to cause significant morbidity, and have been associated with epileptic seizures, intracranial hemorrhage, and focal neurological deficits.2 Management options include non-treatment, surgical resection, and radiosurgery. We review here the efficacy of different management strategies for cavernous malformations and highlight the specific role of radiosurgery. One of the major complications of cerebral cavernous malformations is intracranial hemorrhage. To optimize patient treatment, it is beneficial to be able to identify patients that are at an increased risk of developing a hemorrhage and would most benefit from intervention. The overall rate of hemorrhage in patients with CMs has been estimated to be 2.25%.3 The rate of hemorrhage, however, is significantly affected by the initial symptom presentation. Patients presenting with a hemorrhage have significantly higher rates of rehemorrhage compared to patients presenting due to incidental findings.3,4 Flemming et al. found that patients presenting with hemorrhage had an overall annual rate of hemorrhage of 6.19% compared to patients presenting without hemorrhage of 0.33%. With increasing use of MR imaging, the percentage of cavernous malformations found incidentally approaches 40%.1 Because the risk of hemorrhage is low in patients with CMs found incidentally, surgical or radiosurgery management may not be indicated. In contrast, patients presenting with symptoms of hemorrhage should be considered for therapeutic intervention due to a high risk for subsequent hemorrhage. One option for the management of cavernous malformations is surgical intervention by CM resection. There is conflicting evidence in the literature regarding the effectiveness of CM resection, likely due to different methodologies used for determining efficacy. When post-operative outcomes are compared to pre-operative values, significant improvement is observed as demonstrated by improvements in the modified Rankin scale and decreased annual hemorrhage rate.5,6 However, the results are limited by the fact that studies did not include a control group of patients that did not receive surgery. A recent retrospective study by Moultrie and colleagues compared the outcome of patients treated with surgical to conservative management. Patients who underwent CM resection had worsened short-term disability scores, increased risk of developing intracranial hemorrhage, and new focal neurologic deficits.

Rare Case of Diffuse Spinal Arachnoiditis Following a Complicated Vertebral Artery Dissection

Spinal arachnoiditis (SA) is an extremely rare and delayed complication of intracranial subarachnoid hemorrhage (SAH). SA is an inflammatory process leading to chronic fibrosis of the spinal cord. Possible pathophysiology is a two-staged disease of initial inflammatory reaction secondary to SAH, followed by a “free interval phase” prior to delayed adhesive phase (i.e. SA). The clinical course can be complicated and is the cause of major morbidity.https://jdc.jefferson.edu/neurosurgeryposters/1009/thumbnail.jp

The ARUBA Trial: How Should We Manage Brain AVMs?

BACKGROUND Brain arteriovenous malformations (bAVMs) are abnormal shunts that bypass the capillary bed and directly divert blood from the arterial to the venous circulation, without exchanging nutrients or dissipating the arterial blood pressure. They are thought to be congenital vascular lesions that occur during the late stages of fetal development, however the exact pathogenesis has not been elucidated yet.1 History of hemorrhage, small AVM size, high arterial feeding blood pressure, and deep venous drainage are the main risk factors that increase the likelihood of AVM rupture. According to the American Stroke Association, 1 in 200-500 people have an AVM, while 25% of AVM patients experience seizures and 50% of patients suffer intracranial hemorrhage (ICH) at some point in their lives.2 Also, 5-15% of AVM patients experience severe headaches because of the increased intracranial pressure and a similar percentage of patients exhibit neurological deficits.1 With the advent of noninvasive imaging, AVMs are being detected at an early, unruptured stage, but the optimal course of action for preventing future complications still remains uncertain. The ARUBA trial strove to determine whether medical management or interventional therapy has a better long-term outcome for patients with unruptured AVMs. While it provides important data, limitations in its study design raise doubts concerning the generalizability of its findings. The study planned to include 800 patients who were to be followed for a minimum of five and a maximum of seven years.3 They were randomly assigned to one of two groups, the interventional therapy and medical management group. Patients in the medical management group received only pharmacological therapy for the medical symptoms that they experienced (unless they developed hemorrhage or infarction, in which case they were switched into the other group). Patients in the interventional therapy group received endovascular surgery, microsurgery, or radiosurgery, with or without pharmacological therapy depending on their concurrent medical conditions. The primary hypothesis was that medical management is more effective in the treatment of patients with unruptured bAVMs, the primary endpoint was death or stroke, the secondary endpoint was the quality of life, while the functional outcome status was measured using the Rankin scale.3 Previous studies had shown that early interventional treatment in patients with ruptured bAVMs is necessary and patients did not have major future clinical problems.3 Interventional therapy includes endovascular surgery, which aims to occlude the nidus by delivering liquid embolics or embolic coils via a catheter, microsurgical resection of the AVM, or radiosurgery that induces a vascular injury response resulting in AVM obliteration within 1 or 2 years.1 A multimodal therapy that involves more than one of these interventional procedures can also be performed on certain patients. Furthermore, medical management was shown to be very effective in treating unruptured bAVMs as indicated by the very low rate of future hemorrhage. Yet, based on data from the Columbia University Medical Center, interventional treatment of ruptured AVMs had a significantly greater likelihood of hemorrhage and/or clinical impairment (Rankin score ≥2) than medical management of unruptured AVMs. It is thus imperative to compare the effectiveness of the two methods of treatment only on patients with unruptured bAVMs, since patients who present with an ICH have an already much higher risk of experiencing a subsequent ICH (hazard ratio of 3.6).4 The ARUBA trial is the first study comparing medical management to surgical care on patients with unruptured bAVMs and a Rankin score less than two.

The Use of Prasugrel and Ticagrelor in Pipeline Flow Diversion

Background: Despite the routine clopidogrel/aspirin anti-platelet therapy, complications like thromboembolism, continue to be encountered with PED. We studied the safety and the efficacy of prasugrel in the management of clopidogrel non-responders treated for intracranial aneurysms. Methods: 437 consecutive neurosurgery patients were identified between January 2011 and May 2016. Patients allergic or having \u3c30% platelet-inhibition with a daily 75mg of clopidogrel were dispensed 10mg of prasugrel daily (n=20) or 90mg of ticagrelor twice daily (n=2). The average follow-up was 15.8 months (SD=12.4 months). Patient clinical well being was evaluated with the modified Rankin Scale (mRS) registered before the discharge and at each follow-up visit. To control confounding we used multivariable mixed-effects logistic regression and propensity score conditioning. Results: 26 of 437(5.9%) patients (mean of age 56.3 years; 62 women [14,2%]) presented with a sub-arachnoid hemorrhage. 1 patient was allergic to clopidogrel and prasugrel simultaneously. All the patients receiving prasugrel (n=22) had a mRS\u3c2 on their latest follow-up visit (mean=0.67; SD=1.15). In a multivariate analysis, clopidogrel did not affect the mRS on last follow-up, p=0.14. Multivariable logistic regression showed that clopidogrel was not associated with an increased long-term recurrence rate (odds ratio[OR], 0.17; 95%Confidence Interval [CI95%], 0.01-2.70; p=0.21) neither with an increased thromboembolic accident rate (OR, 0.46; CI95%, 0.12-1.67; p=0.36) nor with an increased hemorrhagic event rate (OR, 0.39; CI95%,0.91-1.64; p=0.20). None of the patients receiving prasugrel deceased or had a long-term recurrence nor a hemorrhagic event, only 1 patient suffered from mild aphasia subsequent to a thromboembolic event. 3 patients on clopidogrel passed during the study: (2) from acute SAH and (1) from intra-parenchymal hemorrhage. Clopidogrel was not associated with an increased mortality rate (OR, 2.18; CI95%,0.11-43.27; p=0.61). The same associations were present in propensity score adjusted models. Conclusion: In a cohort of patients treated with PED for their intracranial aneurysms, prasugrel (10mg/day) is a safe alternative to clopidogrel resistant, allergic or non-responders

Assessing a 600-mg Loading Dose of Clopidogrel 24 Hours Prior to Pipeline Embolization Device Treatment

Background: Clopidogrel/aspirin antiplatelet therapy routinely is administered 7-10 days before pipeline aneurysm treatment. Our study assessed the safety and efficacy of a 600-mg loading dose of clopidogrel 24 hours before Pipeline Embolization Device (PED) treatment. Methods: In this retrospective cohort study, we included patients treated with PED from October 2010 to May 2016. A total of 39.7% (n = 158) of patients were dispensed a loading dose of 650 mg of aspirin plus at least 600 mg of clopidogrel 24 hours preceding PED deployment, compared to 60.3% (n = 240) of patients who received 81-325 mg of aspirin daily for 10 days with 75 mg of clopidogrel daily preprocedurally. The mean follow-up was 15.8 months (standard deviation [SD] 12.4 months). modified Rankin Scale (mRS) was registered before the discharge and at each follow-up visit. To control confounding, we used multivariable logistic regression and propensity score conditioning. Results: Of 398 patients, the proportion of female patients was ~16.5% (41/240) in both groups and shared the same mean of age ~56.46 years. ~12.2% (mean = 0.09; SD = 0.30) had a subarachnoid hemorrhage. 92% (mean = 0.29; SD = 0.70) from the pretreatment group and 85.7% (mean = 0.44; SD = 0.91) of the bolus group had a mRS ≤2. In multivariate analysis, bolus did not affect the mRS score, P = 0.24. Seven patients had a long-term recurrence, 2 (0.83%; mean = 0.01; SD = 0.10) of which from the pretreatment group. In a multivariable logistic regression, bolus was not associated with a long-term recurrence rate (odds ratio [OR] 1.91; 95% confidence interval [CI] 0.27-13.50; P = 0.52) or with thromboembolic accidents (OR 0.99; 95% CI 0.96-1.03; P = 0.83) nor with hemorrhagic events (OR 1.00; 95% CI 0.97-1.03; P = 0.99). Three patients died: one who received a bolus had an acute subarachnoid hemorrhage. The mean mortality rate was parallel in both groups ~0.25 (SD = 0.16). Bolus was not associated with mortality (OR 1.11; 95% CI 0.26-4.65; P = 0.89). The same associations were present in propensity score-adjusted models. Conclusions: In a cohort receiving PED, a 600-mg loading dose of clopidogrel should be safe and efficacious in those off the standard protocol or showing \u3c30% platelet inhibition before treatment

Decompressive Hemicraniectomy: Predictors and Functional Outcome In Patients With Ischemic Stroke

BACKGROUND Patients presenting with large ischemic strokes may develop uncontrollable, progressive brain edema that risks compression of brain parenchyma and cerebral herniation.1 Edema that does not respond to medical treatment necessitates decompressive hemicraniectomy (DH) as a life-saving procedure. The functional outcome of patients is uncertain and the patient’s family is presented with the difficult decision of intervention with DH. While the functional outcome of patients is not worsened by DH,2 neurological deficit is likely as a result of initial large-territory ischemia. The correlation of specific clinical variables preceding DH to patient outcome helps inform clinicians and families about prognosis.3 This study identifies an array of clinical variables in patients who underwent DH for ischemic stroke in order to investigate potential predictors of functional outcome. METHOD A total of 1,624 subjects that underwent any type of craniectomy from 2006 to 2014 were retrospectively screened via electronic medical record. The specific selection criterion was DH secondary to ischemic stroke involving the middle cerebral artery (MCA), internal carotid artery (ICA), or both. Subjects were excluded if they underwent craniectomy for any reason other than DH for ischemic stroke; or if the MCA or ICA were not implicated. The clinical variables that were collected may be divided into pre-DH and post-DH. The pre-DH variables involve patient demographics and past medical history, in addition to clinical variables during the period of presentation and clinical management leading up to DH. The post-DH variables describe the in-patient recovery period and discharge status. The primary outcome was functional status assessed by the Modified Rankin Scale (MRS) score at 90 days post-DH. The MRS ranges from 0 (no symptoms) to 6 (death) with intermediate values (1-5) representing increasing functional and cognitive disability